NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Biotechnology;Cancer;Cancer Genomics;Clinical Research;Data Science;Dental, Oral, and Craniofacial Disease;Drug Abuse (NIDA only);Genetics;HIV/AIDS;Human Genome;Immunotherapy;Infectious Diseases;Microbiome;Networking and Information Technology R&D (NITRD);Prevention;Substance Misuse

PI_NAMEs: CAMERON, MARK JAMES (contact)

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;advanced system;Aftercare;Animal Model;Animals;Area;Basic Science;Bayesian Analysis;Big Data;Bioinformatics;Biological Assay;Biological Markers;Biometry;Biostatistics Core;Blood;Cells;Clinical;Clinical Research;Clinical Sciences;Clinical Trials;cohort;Collaborations;Collection;Complex;Computer Analysis;Consultations;Data;data acquisition;data dissemination;data management;data standards;Databases;deep sequencing;design;design verification;Development;Disease Outcome;Disease Progression;dysbiosis;Experimental Designs;Fostering;Foundations;fundamental research;Gender;Gene Expression Profile;Genetic Transcription;Genomics;high throughput analysis;HIV;HIV Infections;Human;Image;Immune;immune function;immune reconstitution;Immune response;Immune System Diseases;Immunological Models;Immunologics;Immunology;Immunology procedure;Immunotherapeutic agent;Immunotherapy;Inflammation;innovation;interest;Manuscripts;Maps;Metadata;Methodology;microbial;microbiome;microbiome research;microbiota;Mission;Molecular;Molecular Analysis;multidisciplinary;multiple omics;new technology;novel;Outcome;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Preparation;Prevention;Process;Protein Analysis;Protocols documentation;public database;Publications;Reporting;Reproducibility;Research;Research Design;Research Personnel;research study;RNA analysis;Sampling;Services;sex;Shapes;Statistical Data Interpretation;Structure;Support System;Surveys;Systems Biology;Technology;technology platform;Tissue Model;Tissues;tool;Training;Training and Education;transcriptome sequencing;transcriptomics;Translational Research;translational study;Translations;transmission process;treatment response;Virus;Writing

PROJECT_TITLE: Core F:  Systems Biology & Biostatistics


ADMINISTERING_IC: AI

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cancer;Dental, Oral, and Craniofacial Disease;Drug Abuse (NIDA only);HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Prevention;Social Determinants of Health;Substance Misuse;Women's Health Research

ORG_CITY: CLEVELAND

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PI_NAMEs: CAMERON, CHERYL M (contact)

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;AIDS prevention;Anti-Retroviral Agents;Area;Attention;Award;Awareness;Basic Science;Behavior;Behavioral;Behavioral Sciences;Biological;Biology;Caring;Cell model;Cellular biology;cis-female;Clinical;Clinical Management;Clinical Research;Clinical Sciences;Collaborations;Communities;Contraceptive Usage;Coupled;Cross-Sectional Studies;demographics;Development;Disease;Disease Progression;Disparity;Enrollment;Epidemic;Feminization;Fostering;Funding Opportunities;Gender;gender difference;gender disparity;Goals;Gonadal Steroid Hormones;HIV;HIV Infections;HIV-1;Hormonal;Hormones;immune activation;Immune response;Immunity;Immunology;Immunotherapy;improved;In Vitro;Inequity;Infection;Infrastructure;innovation;insight;Institution;Interdisciplinary Study;Investigation;Knowledge;Leadership;lens;Longitudinal cohort;meetings;member;Menopausal Status;Menstrual cycle;Mentors;Mentorship;Methodology;Molecular;Molecular Biology;multidisciplinary;Obesity;Outcome;Pathogenesis;Performance;Persons;Pharmaceutical Preparations;Phase;Population;Predisposition;Prevalence;Prevention;programs;Psychology;Public Health;Reporting;repository;Research;Research Infrastructure;Research Personnel;Resources;response;Risk;Role;Sampling;Scientific Inquiry;sex;Sex Differences;sex disparity;Site;social;socioeconomics;Sociology;Structure;success;synergism;Techniques;transgender;transgender women;treatment response;Universities;Violence;Viral;Viral Pathogenesis;Virus;Work;working group

PROJECT_TITLE: SWG1:  Sex & Gender Working Group


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cancer;Dental, Oral, and Craniofacial Disease;Dissemination and Implementation Research;Drug Abuse (NIDA only);HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Prevention;Substance Misuse

PI_NAMEs: AVERY, ANN K (contact)

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Advocacy;Affect;AIDS clinical trial group;AIDS prevention;Applications Grants;Automobile Driving;Award;Behavioral Research;biobehavior;Biomedical Research;Black race;Clinical;Clinical Trials Unit;Collaborations;Communities;community empowerment;community engagement;community engagement process;Community Health;community research;County;Data;demographics;design;Development;Diagnosis;Dimensions;Education;Epidemic;Event;Fostering;Funding;Gender;Geographic Locations;Geography;Goals;Grant;Growth;Health;HIV;HIV Infections;HIV Vaccine Trials Network;HIV/AIDS;Hour;implementation research;implementation science;Incidence;Institution;inter-institutional;interdisciplinary collaboration;Interdisciplinary Study;Intervention;investigator training;Investments;Joints;Leadership;Link;Medicine;meetings;member;Mentorship;Mission;neighborhood disadvantage;Policies;Policy Maker;Population;population based;pre-exposure prophylaxis;prevent;Prevention;Prevention Research;Privatization;Productivity;programs;Public Health;Recording of previous events;Research;Research Infrastructure;Research Personnel;Research Priority;Research Project Grants;Research Proposals;Research Training;Resources;response;Science;sex;sexual minority community;sexual minority men;shared decision making;Site;social;Structure;success;Training;Underrepresented Minority;United States;United States Dept. of Health and Human Services;United States Health Resources and Services Administration;United States National Institutes of Health;Universities;working group

PROJECT_TITLE: SWG2: End the HIV Epidemic


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Natural Products

ORG_CITY: CLAREMONT

ORG_NAME: SCRIPPS COLLEGE

ORG_STATE: CA

PHR: PROJECT NARRATIVE:  Chemical discovery from nature, including from symbiotic microbes, represents a productive strategy for delivering new antibiotics and other drugs. This proposal seeks to discover active molecules with clinical potential from a niche with high discovery potential, desert Trachymyrmex ants, and to determine how such molecules are distributed across this niche. These findings will provide a framework for efficiently accessing new drug leads from this and related systems.

PI_NAMEs: VAN ARNAM, ETHAN BUGGIE (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: American;analog;Animals;Anti-Bacterial Agents;anti-fungal agents;Antibiotics;Ants;Bacteria;Biological Factors;broadening participation research;Chemical Structure;chemical synthesis;Chemicals;Chemistry;Clinical;clinical predictors;clinically relevant;cohort;Collaborations;Collection;college;Data;Data Analyses;Data Set;Ecology;Environment;Environmental Risk Factor;experience;Faculty;Fractionation;Funding;Future;Genetic;Geographic Factor;Geography;guided inquiry;Habitats;Individual;innovation;Insecta;Institution;instrumentation;Investigation;Laboratories;Laboratory Research;Libraries;Location;Maps;Medicine;metabolomics;Microbe;microbial;Modernization;Molecular;Natural Products;Natural Products Chemistry;Natural Selections;Nature;novel;novel therapeutics;pathogenic microbe;Pharmaceutical Preparations;Predictive Factor;Productivity;Publications;Recording of previous events;recruit;Research;Research Personnel;Research Project Grants;Research Support;Role;sample collection;Sampling;scaffold;Science;screening;Site;STEM career;Structure;Students;Surveys;symbiont;Symbiosis;System;Training;undergraduate student;Underrepresented Populations;Woman;Work

PROJECT_TITLE: Leveraging symbiosis and desert biogeography for discovery of host-selected natural products

STUDY_SECTION: CSB

STUDY_SECTION_NAME: Chemical Synthesis and Biosynthesis Study Section[CSB]


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Nutrition;Obesity;Pediatric;Prevention

ORG_CITY: BALTIMORE

ORG_DEPT: PSYCHIATRY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Our project, RESONATE, aims to investigate why some children develop obesity. To do this it uses data on eating and eating-related behaviors, genetic and environmental factors, and brain structure and function, collected in a sub-sample of RESONANCE, a large study of families of children from infancy through childhood. The results will lay foundations for the development of early interventions to prevent or treat obesity.

PI_NAMEs: CARNELL, SUSAN  (contact);D'SA, VIREN ANDREW;KOINIS MITCHELL, DAPHNE

PROGRAM_OFFICER_NAME: WOO, THERESA TESLOVICH

PROJECT_TERMS: Acceleration;Address;Adult;Age;Appetitive Behavior;Behavior;Behavioral;Behavioral Mechanisms;Body Weight;Brain;Central Nervous System;Child;Childhood;cognitive control;cohort;Corpus striatum structure;cue reactivity;Data;Data Analyses;Data Set;Desire for food;Development;Diet Habits;Dietary Factors;discounting;early childhood;Early Intervention;Eating;Eating Behavior;Environmental Risk Factor;excessive weight gain;Family Study;feeding;Food;food environment;Foundations;Functional Magnetic Resonance Imaging;Funding;Genetic;genetic risk factor;genetic variant;Gliosis;Goals;gray matter;Health;Home;Hypothalamic structure;Individual;individual variation;infancy;Inflammatory Response;Intake;inter-individual variation;Intervention;Lead;Life;Magnetic Resonance Imaging;Measures;Mediating;Metabolic;Methods;middle childhood;myelination;neurobehavioral;Neurological observations;neuromechanism;Obesity;obesity development;obesity in children;obesity prevention;obesity risk;obesogenic;Outcome;Parents;Participant;Pathogenesis;Pattern;Performance;postnatal;pre-clinical research;prenatal;prepregnancy obesity;prevent;protective factors;Reporting;Research;reward processing;Rewards;Risk Factors;Role;Structure;Testing;Time;United States National Institutes of Health;Variant;Weight;Weights and Measures

PROJECT_TITLE: Neural and behavioral mechanisms of obesity development from infancy through childhood

STUDY_SECTION: HSDO

STUDY_SECTION_NAME: Human Studies of Diabetes and Obesity Study Section[HSDO]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cancer;Cannabinoid Research;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Electronic Nicotine Delivery Systems;Lung;Lung Cancer;Natural Products;Prevention;Substance Misuse;Tobacco;Tobacco Smoke and Health

PHR: PROJECT NARRATIVE This project will consist of two studies designed to systematically evaluate the influence of cannabis administration on the motivational effects of the two most commonly used tobacco products (combusted cigarettes and electronic cigarettes) using a rigorous human laboratory design and behavioral economic framework. Results from these studies will document the extent to which, and under what conditions, cannabis use may alter motivation to use tobacco products. Understanding the influence of cannabis on tobacco use across varied routes of administration and a broad nicotine dose range will inform key regulatory policies (e.g. cannabis standard unit dosing and nicotine reduction policies) within the cannabis and tobacco regulatory fields.

PI_NAMEs: LEE, DUSTIN CLARK (contact);STRICKLAND, JUSTIN CHARLES

PROGRAM_OFFICER_NAME: KAUTZ, MARY A

PROJECT_TERMS: Acute;Affect;Automobile Driving;behavioral economics;Cannabinoids;Cannabis;cannabis administration;Cannabis policy;cardiovascular effects;Cigarette;Clinical;combustible cigarette;craving;Data;design;Development;Dose;Drug usage;Elasticity;Electronic cigarette;electronic cigarette use;Ensure;epidemiologic data;Evaluation;experience;Human;Incentives;Laboratories;Laboratory Study;Marijuana Dependence;marijuana use;Marketing;Measures;Moods;Motivation;National Institute of Drug Abuse;Nicotine;nicotine use;Outcome;Outcome Study;Participant;Pattern;Persons;Pharmaceutical Preparations;Pharmacodynamics;physical conditioning;Physiological;Placebos;Policies;polysubstance use;pre-clinical;Prevalence;Price;Procedures;Public Health;public health research;Randomized;Recording of previous events;Reporting;Research;Research Design;response;Rodent;Route;Self Administration;Smoke;Standardization;substance use;Task Performances;Tetrahydrocannabinol;THC exposure;Tobacco;tobacco cessation intervention;tobacco products;tobacco regulatory science;Tobacco use;Tobacco Use Cessation;Tobacco Use Disorder;validation studies;Withdrawal;Work

PROJECT_TITLE: Effect of Cannabinoids on Tobacco Product Demand and Pharmacodynamics

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: NOVATO

ORG_NAME: BUCK INSTITUTE FOR RESEARCH ON AGING

PHR: PROJECT NARRATIVE Senescent cells develop an inflammatory senescence-associated secretory phenotype (SASP) and can also spread from senescent to non-senescent bystander cells in a process known as senescence-induced senescence (SIS). Although neurons were historically considered to be unable to undergo cellular senescence, recent research has suggested that neurons may be able to undergo senescence during normal aging and disease. Using both in vitro human 2D and 3D cell cultures and a newly generated mouse AD model in which senescent cells can be tracked and inducibly eliminated we will determine: (1) the ability of neurons to undergo stress-mediated senescence and a SASP, (2) whether this is accompanied by an Abeta-independent SIS, (3) whether late-stage losses in immune privilege enables clearance of senescent cells via infiltration of peripheral immune cells, and (4) whether senescent cell removal is beneficial or detrimental and at what stage of disease progression.

PI_NAMEs: ANDERSEN, JULIE KAY (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: 3xTg-AD mouse;abeta oligomer;Ablation;age-related disease;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease related dementia;Amyloid beta-Protein;Animal Model;Antibodies;Astrocytes;Automobile Driving;Brain;brain health;Cell Aging;Cell Cycle;cell type;Cells;Clinical Trials;Cognitive;Dementia;Disease;Disease Progression;Excision;Failure;functional improvement;Human;Immune;immune clearance;Impaired cognition;improved;In Vitro;in vivo;Infiltration;Inflammatory;Investments;Laboratories;Ligands;Mediating;Modeling;mouse model;Mus;Natural Killer Cells;Neuroglia;Neurons;neuropathology;normal aging;novel strategies;novel therapeutic intervention;p38 Mitogen Activated Protein Kinase;paracrine;Pathology;Pattern;Peripheral;Pharmaceutical Preparations;Phenotype;postmitotic;prevent;Process;Research;response;Role;senescence;senescence associated secretory phenotype;senescent cell;Senile Plaques;senolytics;Stress;stressor;tau Proteins;tau-1;Temporal Lobe;three dimensional cell culture;Transgenic Mice;Withdrawal

PROJECT_TITLE: Cellular senescence and Alzheimer's disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-A(50)R]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: PORTLAND

ORG_DEPT: PEDIATRICS

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative This proposal focuses on recently discovered mechanisms of impaired regeneration and repair of diffuse human white matter lesions that we propose are central to vascular brain injury and cognitive decline associated with aging and vascular dementia. We will employ pioneering vascular physiology and molecular approaches to define how chronic injury and inflammation of human white matter blood vessels contributes to the progression of white matter injury by studying MRI-defined lesions from human autopsy brains from patients confirmed to have cognitive decline. The role of disrupted white matter blood flow will be related to disrupted maturation of a key brain cell type (the oligodendrocyte progenitor) that appears to play a central role in aberrant brain recovery (remyelination failure) after white matter injury to be defined by MRI.

PI_NAMEs: BACK, STEPHEN ARTHUR (contact)

PROGRAM_OFFICER_NAME: NEWMAN, ELIZABETH

PROJECT_TERMS: Abbreviations;Adhesions;Adult;Age Years;Aging;arteriole;Astrocytosis;Autopsy;Biochemical;Biology;Blood - brain barrier anatomy;Blood capillaries;Blood flow;Blood Vessels;blood-brain barrier disruption;Brain;brain cell;Catabolism;CD44 Antigens;CD44 gene;Cell Aggregation;Cell Differentiation process;Cell Maturation;cell type;Cells;Cerebral Ischemia;Cerebrovascular Disorders;Cerebrovascular Trauma;Cerebrum;Chronic;clinical predictors;Cognitive;cohort;Data;Dementia;Diffuse;Digestion;Elderly;Endothelial Cells;endothelial dysfunction;Endothelium;Extracellular Matrix;Extravasation;Failure;Functional disorder;Generations;Glycosaminoglycans;Human;Hyaluronan;hyaluronan synthase 1;Hyaluronic Acid;Hyaluronidase;Impaired cognition;Impairment;in vitro Model;Individual;Inflammation;Inflammatory;Injury;Investments;Lesion;Link;Lymphocyte;lymphocyte trafficking;Magnetic Resonance Imaging;Mediating;Membrane;Metabolism;Microvascular Dysfunction;Molecular;Molecular Weight;mouse model;multidisciplinary;Mus;Myelin;myelination;Natural regeneration;neuroimaging;neuropathology;Nitric Oxide;Nitric Oxide Synthase;nitrosative stress;nonhuman primate;novel;oligodendrocyte progenitor;Oligodendroglia;oxidative damage;Oxidative Stress;Pathologic;Pathway interactions;Patients;Penetration;Physiology;Play;Predisposition;prevent;Process;Reactive Nitrogen Species;Reactive Oxygen Species;Recovery;remyelination;repaired;Reporting;response;Risk Marker;Rodent Model;Role;Signal Pathway;Signal Transduction;stem cell migration;stem cell proliferation;stem cells;Testing;therapy development;TLR4 gene;vascular cognitive impairment and dementia;Vascular Dementia;Vascular Diseases;Vascular Endothelial Cell;vascular injury;Vascular Permeabilities;Vasodilation;Vasodilator Agents;white matter;White Matter Hyperintensity;white matter injury

PROJECT_TITLE: Oligodendrocyte Progenitors and Hyaluronan-mediated Mechanisms of Human Vascular White Matter Injury

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Autoimmune Disease;Brain Disorders;Dementia;Digestive Diseases;Inflammatory Bowel Disease;Neurodegenerative;Neurosciences

ORG_CITY: GRAND FORKS

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF NORTH DAKOTA

ORG_STATE: ND

PHR: Narrative Alzheimer's disease (AD) is the most common age-associated neurodegenerative disease in the U.S. Since the brain and gastrointestinal tract influence each other, it is important to know whether intestinal dysfunction elevates the risk or progression of AD. Using a mouse model of Alzheimer's disease, we will determine whether basal disease-associated intestinal inflammation contributes to brain presentation of disease and whether exacerbating intestinal dysfunction by inducing inflammatory bowel disease potentiates the severity of brain changes. More importantly, we will determine whether available strategies for modulating intestinal inflammation can prevent its influence on progression of AD. This study will define a new understanding of how AD develops and provide a new therapeutic approach to prevent it.

PI_NAMEs: COMBS, COLIN K (contact)

PROGRAM_OFFICER_NAME: PETANCESKA, SUZANA

PROJECT_TERMS: Age;Age Months;age related;age related neurodegeneration;Aging;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease risk;Amyloid beta-Protein;Antibodies;Antibody Therapy;Anxiety;APP-PS1;Attenuated;Biochemical;blood-brain barrier crossing;blood-brain barrier penetration;blood-brain barrier permeabilization;Brain;brain tract;Cells;Central Nervous System Diseases;Characteristics;Chronic;Clinical;cognitive function;Colitis;Colonic Diseases;Colonic inflammation;combat;Communication;Crohn's disease;cytokine;Data;demented;Deposition;dextran sulfate sodium induced colitis;Disease;Disease Progression;efficacy evaluation;Elderly;experimental study;Fatigue;Feces;Female;Flow Cytometry;Functional disorder;gastrointestinal;Gastrointestinal Diseases;Gastrointestinal tract structure;genetic approach;Gliosis;gut inflammation;gut-brain axis;Histologic;Immune;immune modulating agents;Immune system;Immune System Diseases;immunomodulatory therapies;immunoreactivity;Impairment;Incidence;indexing;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inflammatory marker;innovation;Intervention;Intestinal Diseases;intestinal epithelium;Intestinal Motility;Intestinal permeability;Intestines;Link;lymph nodes;Lymphoid Cell;Macrophage;male;Measures;Mediating;Memory;Memory impairment;Mental Depression;middle age;Modeling;Monitor;Motility;mouse model;Mus;Neurodegenerative Disorders;neurogenesis;Non-Steroidal Anti-Inflammatory Agents;novel therapeutic intervention;null mutation;Patients;Peripheral;Permeability;Peyer's Patches;pharmacologic;Phenotype;Plasma;Positioning Attribute;Predisposition;Prevalence;prevent;Reporting;Retrospective Studies;Risk;Role;Senile Plaques;Severities;Sodium Dextran Sulfate;Spleen;Synapses;T-Lymphocyte;Testing;Therapeutic;Therapeutic Effect;Therapeutic Intervention;Time;Transgenic Mice;Tumor Necrosis Factor-Beta;Ulcerative Colitis;Wild Type Mouse

PROJECT_TITLE: Communicating Intestinal Inflammation to the Brain in Alzheimer's Disease


ORG_CITY: DALLAS

ORG_DEPT: NEUROLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE Alzheimer disease and related tauopathies are major diagnostic, therapeutic, and clinical challenges but new data suggests that conformational ensembles of the tau monomer might hold the key to understanding the basis of clinical diversity. Our study seeks to determine the structure of seed- competent tau monomer (which self-assembles and serves as a template for fibril growth), to test the relationship of tau monomer conformation to the conformation of larger assemblies. This will greatly advance our ability to classify diseases, potentially using tau monomer recovered from biofluids, and to develop more personalized therapies.

PI_NAMEs: DIAMOND, MARC I (contact);JOACHIMIAK, LUKASZ A.

PROGRAM_OFFICER_NAME: YANG, AUSTIN JYAN-YU

PROJECT_TERMS: accurate diagnosis;Alzheimer's Disease;Amino Acids;amyloid structure;Animal Model;Biosensor;Brain;brain cell;Cell Culture Techniques;Cell model;Cells;Chemicals;Classification;Classification Scheme;Clinical;Consensus;crosslink;Crosslinker;Cryoelectron Microscopy;Data;Diagnosis;Diagnostic;disease classification;Disease Progression;Generations;Grain;Grant;Growth;Human;Individual;Induced pluripotent stem cell derived human neuron;Mass Spectrum Analysis;Methods;Modeling;Molecular Conformation;molecular modeling;monomer;Mus;Mutation;Neurons;neuropathology;novel;Organism;Pathology;Patients;Pattern;personalized medicine;Point Mutation;Prions;Protein Region;Publications;Recombinants;self assembly;Solvents;structural biology;Structure;System;tau aggregation;tau conformation;tau Proteins;Tauopathies;Testing;Therapeutic;Transgenic Organisms;transmission process;unpublished works;Work

PROJECT_TITLE: Seeds and Strains Derived from Tau Monomer

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Genetics;Neurodegenerative;Neurosciences;Women's Health Research

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Biologic sex influences Alzheimer's disease (AD) and how sex chromosomes – and specifically the second X chromosome – plays a role is largely unknown. Females have two X chromosomes and males have one. However, since one X inactivates in females, X dose is largely similar between the sexes. This proposal focuses on how Kdm6a, a conserved and robust escapee of X chromosome inactivation, contributes sex difference and confers resilience to AD-related measures in cells, mouse models, and human populations. The expected impact of our innovative studies is that they will fundamentally advance our mechanistic understanding of how the second X chromosome causes sex difference related to AD using an approach that integrates cellular, mouse and human studies. The new understanding of X contribution to sex difference will pave pathways to urgently needed treatments for both men and women.

PI_NAMEs: DUBAL, DENA BOU (contact)

PROGRAM_OFFICER_NAME: CHAKROBORTY, SHREAYA

PROJECT_TERMS: Acute;Aging;Alzheimer's Disease;Alzheimer's disease risk;Amyloid beta-Protein;Area;arm;Biological;Biological Markers;biological sex;Biology;Brain;brain health;Cell model;cell type;Cells;Cessation of life;Classification;Clinical;Cognition;Cognitive;Cognitive deficits;Cytoplasm;Data;Development;Disease;Dose;Environment;experience;Female;Gender;gene product;Genes;Genetic Models;genetic variant;Genetic Variation;gonad development;Grant;Heterogeneity;Hippocampus;Human;human old age (65+);Image;Impaired cognition;In Vitro;in vivo;Incidence;Individual;innovation;lifetime risk;Link;Longevity;loss of function mutation;male;Measures;Mediating;men;Molecular;mortality;mouse model;Mus;Nerve Degeneration;neural;Neurons;Nuclear;Pathogenicity;Pathology;Pathway interactions;Play;Population;Proteins;Proxy;resilience;Risk;Risk Factors;Role;sex;Sex Chromosomes;Sex Differences;Shapes;Source;Structure;Synapses;Synaptic plasticity;Testing;Toxic effect;Variant;Woman;women versus men;X Chromosome;X Inactivation;Y Chromosome

PROJECT_TITLE: Mechanisms of X-Chromosome-dependent Sex Difference inAlzheimers Disease

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Neurodegenerative;Neurosciences

ORG_CITY: NEW YORK

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: Oligomers of the protein tau are thought to be key contributors to the death of brain cells in Alzheimer's disease, but we don't know their structures. Here we propose to determine, for the first time, the structure of a toxic oligomeric form of tau. Because tau function, aggregation and toxicity are modulated by covalent modifications, we also aim to clarify how such modifications influence tau function and tau oligomers.

PI_NAMEs: ELIEZER, DAVID  (contact)

PROJECT_TERMS: Acetylation;Adopted;Affect;Alzheimer's Disease;Alzheimer's disease brain;Amyloid;Amyloid Fibrils;Appearance;Binding;Biological Assay;Brain;brain cell;brain control;Cell Death;Cell membrane;Cell model;Cells;Cessation of life;Characteristics;chronic traumatic encephalopathy;Cognition Disorders;Dementia;Deposition;Development;Disease;Disease Progression;Electron Spin Resonance Spectroscopy;Etiology;Frontotemporal Dementia;Goals;Impaired cognition;In Vitro;Intervention;Length;Location;Lysine;Maps;Measurement;Mediator;Membrane;Methods;Microtubules;Modification;Molecular Conformation;monomer;Mutation;Nerve Degeneration;Neurofibrillary Tangles;neuron loss;Neurons;NMR Spectroscopy;novel;Pathologic;Peptides;Phosphorylation;Physiological;Pick Disease of the Brain;Post-Translational Protein Processing;Post-Translational Regulation;Property;Protein Isoforms;protein oligomer;Resolution;Role;self assembly;Site;solid state nuclear magnetic resonance;stathmin;Structure;success;targeted treatment;tau aggregation;tau function;tau interaction;tau microtubule binding domain;tau Proteins;tau-1;tau-microtubule interaction;Time;Titrations;Toxic effect;Tubulin;Work

PROJECT_TITLE: Structure and Function of Tau


ORG_CITY: OKLAHOMA CITY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Accumulation of cells undergoing senescence during aging compromises tissue function; astrocytes, critical for brain function, display markers of senescence in Alzheimer’s disease (AD). We discovered that pathogenic tau protein causally implicated in AD potently induces senescence by its transmission to astrocytes. By defining the role of pathogenic tau-induced astrocyte senescence in AD we will open up a completely new avenue of investigation that will contribute urgently needed tools to treat AD and potentially other dementias.

PI_NAMEs: GALVAN, VERONICA  (contact);VAN REMMEN, HOLLY

PROJECT_TERMS: abnormally phosphorylated tau;Address;aged;Aging;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease risk;Antibodies;Architecture;Area;Astrocytes;biochemical tools;Biological;Brain;Callithrix;Cell Aging;Cell Cycle Arrest;Cell division;cell injury;Cells;cellular development;Clinic;Cytometry;Cytoskeleton;Data;Dementia;Dendritic Spines;density;Disease Progression;Etiology;Event;Excision;FDA approved;Functional disorder;Future;Gene Expression Profiling;Health;Histopathology;Human;hyperphosphorylated tau;immunocytochemistry;Immunotherapy;Impaired cognition;in vivo;Incidence;Inflammatory;innovation;Investigation;Knowledge;Life;Link;live cell microscopy;Microtubule Stabilization;Microtubules;Molecular;Molecular Abnormality;Molecular Sequence Alteration;mouse model;Mus;Nervous System Physiology;Neuroglia;Neuronal Dysfunction;Neurons;nonhuman primate;novel;Onset of illness;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Pharmaceutical Preparations;Population;postmitotic;preservation;Proteomics;Reporting;Research;Role;senescence;senescence associated secretory phenotype;senescent cell;senolytics;Synapses;targeted treatment;tau aggregation;tau mutation;tau Proteins;Tauopathies;Testing;Therapeutic;Time;Tissues;tool;Toxic effect;translational potential;transmission process;Veronica;Work

PROJECT_TITLE: Tau-induced astrocyte senescence in Alzheimer's disease


PHR: PROJECT NARRATIVE. Molecular chaperones maintain the delicate balance of tau levels; however, this process becomes dramatically disrupted in tauopathies. By better understanding the mechanisms of molecular chaperone action, we expect to uncover new ways of treating tauopathies.

PI_NAMEs: CRAIK, CHARLES SCOTT;GESTWICKI, JASON E (contact);SOUTHWORTH, DANIEL RYLAND

PROJECT_TERMS: Affinity;Agonist;Alzheimer's Disease;Alzheimer's disease patient;Animals;Architecture;Attention;Binding;Binding Sites;Biochemical;Brain;C-terminal;Cells;Chemicals;Client;Collaborations;combinatorial;Complex;corticobasal degeneration;Cryoelectron Microscopy;Crystallography;design;Development;Disease;Engineering;Ensure;Enzymes;Equilibrium;FK506 binding protein 5;Genetic;Goals;Heat-Shock Proteins 70;Heat-Shock Proteins 90;hyperphosphorylated tau;improved;Individual;inhibitor;innovation;Laboratories;Learning;Libraries;Location;Maps;MAPT gene;Measures;Modeling;Modification;Molecular;Molecular Chaperones;Nerve Degeneration;Neurodegenerative Disorders;Neurofibrillary Tangles;Neurons;new therapeutic target;novel therapeutics;Pathologic;Peptide antibodies;Peptide Library;Peptidylprolyl Isomerase;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Play;Post-Translational Protein Processing;PP5 protein-serine-threonine phosphatase;Process;Progressive Supranuclear Palsy;Proline-Rich Domain;protein aminoacid sequence;Protein Dephosphorylation;Protein phosphatase;protein protein interaction;Proteins;Proteomics;proteostasis;Quality Control;recruit;Role;Scanning;Solubility;Structure;tau aggregation;tau conformation;tau interaction;tau Proteins;tau-1;Tauopathies;Tertiary Protein Structure;tissue-factor-pathway inhibitor 2;ubiquitin-protein ligase;Ubiquitination;Work

PROJECT_TITLE: Probing the Role of Chaperone-TPR Complexes in Tau Proteostasis

STUDY_SECTION: MSFB

STUDY_SECTION_NAME: Macromolecular Structure and Function B Study Section[MSFB]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Digestive Diseases;Microbiome;Neurodegenerative;Neurosciences

ORG_CITY: WORCESTER

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: PROJECT NARRATIVE Alzheimer's disease (AD) is the most frequent causes of dementia of which there is no cure and treatment options are limited. Recently the human gut microbiome, the community of microorganisms that live within our intestines, has been connected to several neurodegenerative disorders, however this research among AD elders has been limited. Accordingly, our goal is to compare the microbiome of elders with AD to those without dementia, living in different settings, to determine the role the microbiome plays in cognitive decline while studying local and systemic immune function and brain cellular activity. Understanding how the intestinal microbiome impacts AD development and progression will provide novel therapeutic targets and enable future trials aimed at improving the memory of patients with AD.

PI_NAMEs: HARAN, JOHN PATRICK (contact)

PROGRAM_OFFICER_NAME: ARUNKUMAR, NANDINI

PROJECT_TERMS: ABCB1 gene;Address;Affect;Alzheimer's Disease;Alzheimer's disease patient;Anti-Inflammatory Agents;Back;Bacteria;Bacterial Infections;behavioral study;Biological Assay;Biological Models;Brain;Butyrates;cerebral amyloidosis;Characteristics;Chronic;Cognition;cohort;Colon;Communities;community setting;comparative;cytokine;Dementia;Development;Disease Progression;dysbiosis;Elderly;Enrollment;Environment;Epithelium;Etiology;experience;Functional disorder;Future;gene function;genome sequencing;Geriatric Assessment;Goals;gut inflammation;gut microbiome;Home;Homeostasis;Homes for the Aged;Human;immune function;immunosenescence;Impaired cognition;improved;in vivo;Inflammation;Inflammatory;inflammatory marker;intestinal epithelium;intestinal homeostasis;Intestines;Link;Mediator;Memory;Metabolic;Metabolic Pathway;metabolomics;microbial;microbiome;microbiome analysis;microbiome composition;microbiome research;microbiota;microbiota-gut-brain axis;Microglia;microorganism;Monitor;Mus;Neurodegenerative Disorders;new therapeutic target;Nursing Homes;Pathogenesis;Pathway interactions;Patients;Pattern;Play;Population;Prevalence;Production;Property;Publishing;reconstitution;Research;Research Support;Role;Sampling;stool sample;systemic inflammatory response;T-Lymphocyte;Taxonomy;Testing;theories;Time;whole genome;Work

PROJECT_TITLE: Understanding the Microbiome-gut-brain axisn Alzheimer disease and its Role in Cognitive Decline


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Brain Disorders;Complementary and Integrative Health;Dementia;Dietary Supplements;Neurodegenerative;Neurosciences;Nutrition

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Narrative This project will examine the protective effects of dietary taurine supplementation in a mouse model of Alzheimer’s disease. The project will examine multiple components of taurine metabolism and brain uptake using magnetic resonance imaging techniques (MRI). We will also compare MRI and positron emission tomography (PET) techniques and measures of inflammation with a battery of pathologic measurements to determine how well the taurine is working. The end result of the project should be a better understanding of the role of taurine in the brain and good test of a novel therapeutic that would be readily applicable to human populations.

PI_NAMEs: DEDEOGLU, ALPASLAN ;JENKINS, BRUCE G (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: age related neurodegeneration;Aging;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Amino Acids;Amyloid beta-Protein;Anti-Inflammatory Agents;Area;Autopsy;Behavior;behavior test;Benign;Brain;Brain Diseases;Brain region;brain tissue;cohort;Cysteine;cytokine;Data;Development;dietary;Dietary Supplementation;dietary supplements;Disease Marker;Disease Progression;Dose;Economic Burden;Etiology;family burden;Glial Fibrillary Acidic Protein;Grant;Hippocampus;Human;imaging biomarker;Imaging Techniques;In Vitro;in vivo;in vivo imaging;Incidence;Inflammation;Inflammatory;inflammatory marker;inflammatory modulation;Interleukin-1;Label;Life Style;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Measurement;Measures;Metabolic;Metabolism;Microglia;microPET;mild cognitive impairment;mouse model;Mus;neurochemistry;neuroinflammation;Neurons;neuropathology;neuroprotection;novel therapeutics;Osmoregulation;Pathologic;Pathology Report;pharmacologic;Plasma;Play;Population;Positron-Emission Tomography;prevent;Process;Property;protective effect;Role;side effect;Societies;Specimen;Stains;Stroke;Supplementation;Symptoms;Taurine;Techniques;Testing;theranostics;Therapeutic Effect;Tissue Sample;Tissues;translation to humans;translational study;Traumatic Brain Injury;uptake;water maze

PROJECT_TITLE: Protective roles of taurine in Alzheimer's disease brain

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SANTA BARBARA

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA BARBARA

PHR: Project Narrative Aging and Alzheimer’s disease are often inextricably linked; however, in cases with certain mutations the disease onset occurs early and before the changes of advanced age set in. We will compare a very large sample of brains that all harbor the same early onset Alzheimer gene mutation— PSEN1[E280A] to sporadic age-related disease. We propose a complete neuropathological analysis of this invaluable resource and the development of cellular models from living cells with this mutation.

PI_NAMEs: KOSIK, KENNETH STEPHEN (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: Acetylation;Affect;Age;age related;age related changes;age-related disease;Aging;alpha synuclein;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Amyloid;Antibodies;Astrocytes;Astrocytosis;Attention;Autopsy;Brain;brain control;Cell Aging;Cell Differentiation process;Cell model;Cell Nucleus;cell type;Cells;cellular development;Cerebrovascular system;Characteristics;Coculture Techniques;Collaborations;Collection;Colombia;Colombian;Complex;complex data;CSPG4 gene;cytokine;Cytoplasm;Data;Data Set;Defect;Disease;Dominant Genetic Conditions;early onset;Early Onset Alzheimer Disease;Elderly;experience;Extravasation;familial Alzheimer disease;Family;Fibroblasts;Gene Expression;Gene Mutation;Genes;genome wide association study;glial activation;Glial Fibrillary Acidic Protein;Gliosis;Human;human induced pluripotent stem cells;Image;immunocytochemistry;Immunohistochemistry;Individual;Induced pluripotent stem cell derived human neuron;Inflammation;Inflammatory;inflammatory marker;Institution;Interleukin-1 alpha;Interleukin-1 beta;Interleukin-6;International;Link;Literature;loss of function;Maryland;Mediating;Mendelian disorder;Methods;Microglia;Microscopy;Modification;Mutation;neuroinflammation;Neurons;neuropathology;New York;novel;Nuclear;Nuclear Envelope;Older Population;Onset of illness;Pathology;Pathway interactions;Patients;PECAM1 gene;Pericytes;Phenotype;Phosphorylation;Population;Positron-Emission Tomography;Preparation;presenilin-1;Prevention trial;programs;protein TDP-43;Publishing;Recording of previous events;Research;Resources;response;Role;Sampling;single cell analysis;single-cell RNA sequencing;Smooth Muscle Myocytes;Statistical Data Interpretation;Sumoylation Pathway;Synapses;synaptic function;synuclein;System;tau Proteins;Techniques;Testing;Text;Tissue Banks;Tissues;TNF gene;tomography;Travel;TREM2 gene;Ubiquitination;United States National Institutes of Health;Universities;Variant;Vascular Smooth Muscle;Visit;Work

PROJECT_TITLE: The complex interaction between Alzheimer drivers and aging


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Genetics;Human Genome;Neurodegenerative;Neurosciences

PHR: Project Narrative Tau is a multi-functional protein that plays a crucial role in several neurodegenerative diseases, including Alzheimer’s disease. One of the more recently identified functions of Tau is regulating chromatin structure and transcriptional regulation; however, how disruptions of these function contribute to the pathology of the diseases is still mostly unknown. To address this gap in knowledge, we will use our novel Drosophila knock-in models to investigate effects of disease-associated Tau on DNA damage responses, chromatin structure, and the neuronal transcriptome.

PI_NAMEs: KRETZSCHMAR, DORIS  (contact)

PROJECT_TERMS: Address;Affect;Age;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Apoptosis;Axon;Behavioral;Binding;Binding Proteins;Binding Sites;candidate selection;Cell Aging;Cell Cycle;Cell Cycle Arrest;Cell membrane;Cell Nucleus;Cells;Chromatin;Chromatin Structure;Chromosome 17;Complex;Data;Development;Disease;Disease Progression;disease-causing mutation;DNA Damage;Drosophila genus;ds-DNA;experimental study;fly;FTD with parkinsonism;Genes;Genetic;Genetic Transcription;Genome;Heterochromatin;heterochromatin-specific nonhistone chromosomal protein HP-1;Human;hyperphosphorylated tau;Impairment;insight;knock-down;Knock-in;Knowledge;Lead;Link;Lipid Binding;Literature;MAPT gene;Memory;Microtubules;Mitochondria;model organism;Modeling;mutant;Mutation;Nerve Degeneration;Neurodegenerative Disorders;neurodegenerative phenotype;Neurofibrillary Tangles;Neuronal Dysfunction;Neurons;novel;Nuclear;Outcome;overexpression;paired helical filament;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Phenotype;Phosphorylation;Phosphotransferases;Play;Point Mutation;prevent;protein aggregation;Proteins;public health relevance;Radiation;Radiation Induced DNA Damage;Regulation;response;Role;segregation;Signal Transduction;single cell ATAC-seq;Single-Stranded DNA;Stress;Structure;Synaptic plasticity;System;tau aggregation;tau function;tau mutation;tau Proteins;tau-1;Tauopathies;Testing;Therapeutic Intervention;Time;Transcriptional Regulation;transcriptome;transcriptome sequencing;Transgenic Organisms;treatment strategy

PROJECT_TITLE: Connecting nuclear functions of Tau with pathology in Alzheimer's disease and other Tauopathies


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: INDIANAPOLIS

ORG_DEPT: GENETICS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Project Narrative Although the central hypothesis in AD states that deposition of amyloid-β (Aβ) plaques is the primary event that facilitates subsequent neurofibrillary tangle (NFT) pathology and neuronal loss, there is no clear understanding of the mechanisms of Aβ-driven neurodegenerative signaling. This proposal aims to investigate how microglial CX3CR1 signaling shapes the neurodegenerative milieu by triggering the accumulation of toxic Aβ species which in-turn facilitate Aβ-driven neurotoxic mechanisms, including the propagation of neurotoxic tau. This study will have critical implications in designing therapeutic approaches to deplete toxic Aβ species in patients with prodromal AD/MCI to slow down or arrest long-term neurodegeneration and cognitive decline.

PI_NAMEs: LAMB, BRUCE T (contact);MEYER, JASON STEPHEN

PROJECT_TERMS: abeta accumulation;abeta deposition;abeta oligomer;Ablation;Acceleration;AD transgenic mice;Affect;Age Months;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease risk;Amyloid;Amyloid beta-Protein;Astrocytes;attenuation;Autopsy;Axon;behavior test;Brain;Coculture Techniques;Cognitive;cognitive change;Communication;confocal imaging;CRISPR/Cas technology;CX3CL1 gene;Data;Dementia;Deposition;design;Disease;disease phenotype;DLG4 gene;Dorsal;Down-Regulation;Electron Microscopy;Electrophysiology (science);Event;extracellular;Flow Cytometry;fractalkine receptor;Functional disorder;Generations;Genes;genetic analysis;Genetic Screening;genome wide association study;glial activation;Health;high resolution imaging;Hippocampus;Histology;Homeostasis;Human;human induced pluripotent stem cells;hyperphosphorylated tau;immune activation;Immunologics;Impaired cognition;Impairment;In Vitro;in vitro Assay;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Inflammatory;Injections;Innate Immune Response;insight;Kinetics;Ligands;lipid metabolism;loss of function;Microglia;Modeling;mouse model;Mus;Mutation;Nerve Degeneration;Neurites;neurofibrillary tangle formation;Neurofibrillary Tangles;Neuroglia;Neuroimmune;neuroinflammation;neuron loss;Neurons;neuroprotection;neurotoxic;neurotransmission;NR1 gene;Outcome;Pathogenesis;Pathologic;Pathology;Pathway Analysis;Pathway interactions;Patients;Phagocytes;Phagocytosis;presenilin-1;prodromal Alzheimer's disease;Quantitative Reverse Transcriptase PCR;receptor;Reporting;Resolution;response;Role;sarkosyl;Senile Plaques;Shapes;Signal Transduction;single nucleus RNA-sequencing;Sorting;Staging;Synapses;Synapsin II;tau function;tau Proteins;Tauopathies;Technology;Testing;Therapeutic;Tissues;Toxic effect;transcriptome sequencing;Up-Regulation;Variant;Western Blotting

PROJECT_TITLE: Deciphering the role of CX3CR1 in Modulating Mechanisms of Amyloid driven Neurodegeneration in Alzheimer's Disease

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Narrative Alzheimer’s disease (AD) is the most common cause of dementia, and the biological processes subserving the disease are not understood. We will investigate how the disease alters energy metabolism necessary for the immune response that exacerbates disease progression. These studies will inform the development of new therapeutics targeting immune cells in the AD brain.

PI_NAMEs: LANDRETH, GARY E. (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: Adipose tissue;aerobic glycolysis;Affect;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease patient;Amyloid deposition;Anions;antagonist;Attenuated;Automobile Driving;Behavior;Binding;Bioenergetics;Biological Process;Blood - brain barrier anatomy;Brain;Catalytic Domain;Cell Reprogramming;Cell Respiration;cell type;Cells;Cellular Metabolic Process;Central Nervous System;Cessation of life;cognitive function;cytokine;Cytoplasm;Data;Dementia;Development;Disease;Disease Progression;efficacy evaluation;Energy Metabolism;Enzymes;Exhibits;Gene Expression Profile;Gene Expression Profiling;Generations;glial activation;Glucose;Glycolysis;Glycolysis Induction;Glycolysis Inhibition;Goals;hexokinase;Hexokinase 2;Housekeeping;hTau Mice;Immune;immune activation;Immune response;Immune Targeting;in vivo;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Intervention;Ischemic Brain Injury;knock-down;Lesion;Lonidamine;Mediating;Metabolic;metabolic abnormality assessment;Metabolism;Microglia;migration;minimal risk;Mitochondria;Morphology;mouse model;Mus;neglect;neurodegenerative phenotype;Neurons;new therapeutic target;novel strategies;Oxidative Phosphorylation;Pathogenesis;Pathology;Patients;Phagocytosis;pharmacologic;Phenotype;Phosphorylation;Play;prevent;Process;Production;Proliferating;Protein Isoforms;Regulation;Reporting;response;Role;selective expression;Senile Plaques;side effect;Signal Pathway;skeletal tissue;small molecule;therapeutic evaluation;therapeutic target;Tissues;TREM2 gene

PROJECT_TITLE: Microglial hexokinase 2 as a therapeutic target in Alzheimer's disease

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative The mechanism underlying memory loss in Alzheimer’s disease is not fully understood. This project examines the role of hippocampal neurogenesis in the engram in familial Alzheimer’s disease and the effect of augmented neurogenesis on restoration of learning and memory.

PI_NAMEs: LAZAROV, ORLY  (contact)

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: Address;Affect;Alzheimer's Disease;Attenuated;Bromodeoxyuridine;Cell Separation;Cells;Cognitive;Cognitive deficits;conditioned fear;Corn Oil;dentate gyrus;design;Deterioration;Diagnosis;Disease;efficacy evaluation;examination questions;Experimental Designs;experimental study;familial Alzheimer disease;FOS gene;Gene Deletion;Genetic;Genetic Recombination;Hippocampus;Human;Impairment;improved;Knock-in Mouse;Label;LacZ Genes;Learning;Mediating;Memory;memory acquisition;Memory impairment;Memory Loss;memory recognition;memory retrieval;mild cognitive impairment;Molecular;mouse model;Mus;nerve stem cell;nestin protein;neurogenesis;Neurons;optogenetics;Pathologic;Patients;Performance;Play;prevent;programs;recruit;restoration;Role;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Survival Rate;Tamoxifen;Techniques;Testing;Transgenes;Virus

PROJECT_TITLE: Plasticity circuits in Alzheimer s disease


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Prevention;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: ANN ARBOR

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: NARRATIVE The proposed research is relevant to public health because the discovery of the biological mechanisms contributing to post-stroke cognitive decline and Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) is ultimately expected to lead to new vascular interventions that protect the cognitive health of Americans. The proposed research is relevant to the part of NIH’s mission of developing fundamental knowledge that will help enhance the health of older adults and reduce the burdens of human disability.

PI_NAMEs: LEVINE, DEBORAH ALLISON (contact)

PROGRAM_OFFICER_NAME: GHALEH, MARYAM X

PROJECT_TERMS: Address;adjudication;Adult;Affect;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;American;Arteries;Automobile Driving;Biological;Biological Factors;Biology;Blood Pressure;Blood Vessels;brain health;Cardiovascular Diseases;cardiovascular disorder risk;Cholesterol;Chronic Disease;Clinical;clinical care;clinical practice;Clinical Research;Clinical Trials;Cognition;Cognitive;cohort;Cohort Studies;Computer Simulation;cost;Data;dementia risk;design;Development;Diabetes Mellitus;disability;effective therapy;Epidemiology;Glucose;Glycosylated Hemoglobin;Goals;Health;Health Policy;Hemorrhage;High Prevalence;Human;Hypertension;Impaired cognition;improved;Incidence;Individual;innovation;Intervention;Intervention Trial;Ischemia;Ischemic Stroke;Knowledge;LDL Cholesterol Lipoproteins;Lead;Lipids;Low-Density Lipoproteins;Measurement;Measures;Methods;Mission;Modeling;models and simulation;novel;older adult;Outcome;Participant;Pharmaceutical Preparations;Policies;Population Heterogeneity;Populations at Risk;post stroke;post stroke cognitive impairment;post stroke dementia;Prevention;Prevention approach;preventive intervention;Prospective cohort;Public Health;public health priorities;Public Policy;Race;racial difference;Research;Risk;Risk Factors;Risk Reduction;Sample Size;Science;sex;Sex Differences;Specific qualifier value;Stroke;stroke event;stroke survivor;Subgroup;Testing;therapy design;Translating;Treatment Factor;trial design;United States National Institutes of Health;vascular contributions;vascular risk factor

PROJECT_TITLE: The Effect of Vascular Risk Factors on Risk of Alzheimer's Disease and Related Dementias after Stroke (STROKE COG)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-F(56)R]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cerebrovascular;Dementia;Lung;Neurodegenerative;Neurosciences;Rehabilitation;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE Stroke-induced respiratory dysfunction is a common sequelae of stroke that contributes to increased cognitive impairment and mortality, yet the cellular and molecular basis of stroke-induced respiratory problems are unknown. Stroke is also common in Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA) patients. This project will establish an aged mouse model of ischemic stroke that can be used to explore both the physiology of post-stroke respiratory dysfunction and to evaluate the efficacy of treatments that target breathing to improve cognitive function in stroke, in AD and CAA patients.

PI_NAMEs: LI, JUN  (contact);MCCULLOUGH, LOUISE D.

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: Acceleration;Affect;Age;age-related disease;aged;Aging;aging population;Alzheimer's Disease;Alzheimer's disease model;Amyloid;amyloid pathology;Animal Model;animal old age;Apnea;Area;Astrocytes;astrogliosis;Blood Vessels;Brain;Brain Stem;Breathing;Cell Nucleus;Cerebral Amyloid Angiopathy;Cerebrum;Chemoreceptors;Cognition;Cognitive;Cognitive deficits;cognitive function;cognitive recovery;Data;Development;disability;Disease Progression;efficacy evaluation;Frequencies;Functional disorder;Gliosis;human old age (65+);Impaired cognition;Impairment;improved;Incidence;infancy;Infarction;inhibitor;Injections;Intervention;Ischemic Stroke;knock-down;Link;Long term disability;Mediating;Mediator;Middle Cerebral Artery Occlusion;Modeling;Molecular;mortality;Motor;motor deficit;mouse model;Mus;Nerve Degeneration;neurovascular;normal aging;old mice;Pathology;Patients;Periodicals;Peripheral;pharmacologic;Phenotype;Physiological;Physiology;post stroke;Prevalence;receptor;Recovery;Reflex action;Regulation;Respiration;Respiration Disorders;respiratory;Secondary to;Serum;Severities;sex;Sex Differences;Signal Transduction;Source;Stroke;stroke cognitive outcome;stroke incidence;stroke model;stroke patient;stroke therapy;Survivors;Tg2576;Therapeutic;therapy design;Tidal Volume;Time;Transforming Growth Factor beta;Transgenic Mice;Treatment Efficacy;United States;Vascular Diseases;ventilation;Work;β-amyloid burden

PROJECT_TITLE: Stroke Disordered Breathing and its Impact on Cognitive Decline in Aging,  Alzheimer's Disease and Cerebral Amyloid Angiopathy


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Prevention

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Project Narrative Due to the lack of approaches for curing Alzheimer’s disease (AD) or slowing down its progression, identifying risk factors or preclinical symptoms and understanding the mechanisms underlying their interactions are of critical importance to early diagnosis and preventative effort. This project aims to reveal the pathophysiological mechanisms underlying the APOE-4-induced olfactory deficit at the anterior olfactory nucleus level and potentially sheds light on developing new approaches for early diagnosis of AD.

PI_NAMEs: LIU, SHAOLIN  (contact)

PROJECT_TERMS: accurate diagnosis;Affect;Alleles;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease pathology;Amygdaloid structure;Amyloid beta-Protein;Animal Disease Models;Animal Model;Animals;Anterior;Apolipoprotein E;apolipoprotein E-4;Behavior;behavior test;Behavioral;Brain;brain tissue;Cells;Clinical;Clinical Research;Cognitive;Data;Dementia;design;Development;Differential Diagnosis;Disease;disease prognosis;Early Diagnosis;Early identification;Electrophysiology (science);Emotional;entorhinal cortex;Ethics;Exhibits;familial Alzheimer disease;Functional disorder;Genes;genetic risk factor;Genotype;Glutamates;Hippocampus;Human;Hyperactivity;hyperphosphorylated tau;Impairment;improved;In Vitro;in vivo;Incidence;Individual;Knowledge;Late Onset Alzheimer Disease;Lateral;Medical;Memory;mild cognitive impairment;Mutation;Nerve Degeneration;neural;neural circuit;Neurodegenerative Disorders;Neurofibrillary Tangles;neuronal excitability;Neurons;neuropsychiatric disorder;new technology;novel strategies;olfactory bulb;Olfactory dysfunction;olfactory nuclei;Olfactory Pathways;optogenetics;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;Peripheral;piriform cortex;Play;Population;Positioning Attribute;pre-clinical;Predisposition;prodromal Alzheimer's disease;Production;prognosis biomarker;Progressive Disease;Psyche structure;Quality of life;Research;Risk Factors;Role;Sampling;Senile Plaques;Severities;Severity of illness;Smell Perception;social;Societies;Structure;Symptoms;Synapses;tau Proteins;tau-1;Testing;Transgenic Animals;Transgenic Mice;transmission process;Work

PROJECT_TITLE: Cellular and circuit mechanisms underlying APOE-4 effects on olfaction.

STUDY_SECTION: CSS

STUDY_SECTION_NAME: Chemosensory Systems Study Section[CSS]


NIH_SPENDING_CATS: Bioengineering;Building Research Capacity at Institutions with Limited NIH Funding;Nanotechnology

ORG_CITY: CHARLOTTE

ORG_DEPT: PHYSICS

ORG_NAME: UNIVERSITY OF NORTH CAROLINA CHARLOTTE

ORG_STATE: NC

PHR: PROJECT NARRATIVE Proteins with luminescence in the visible range are the indispensable tool of biological research. We investigate a new class of luminescent protein-metal complex materials, and elucidate the mechanism of the luminescence to fully develop this emerging technological opportunity. The identified mechanism will be applied for discovering new luminescent protein materials and designing new luminescent peptides, as the new tools with broad utility including in imaging, nanomedicine, and sensing.

PI_NAMEs: EGUSA, SHUNJI  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Acceleration;Affect;Amino Acid Motifs;Amino Acids;Attention;Binding;Binding Sites;Biocompatible Materials;Bioinformatics;Biological;biological research;Biomedical Research;Bovine Serum Albumin;Catalysis;Cations;Chemistry;Color;Complex;cysteinylcysteine;design;Disparate;disulfide bond;Electronics;Emerging Technologies;Engineering;Environment;Exhibits;experience;experimental study;Future;Goals;Gold;Green Fluorescent Proteins;Image;Kinetics;knowledge of results;Ligand Binding;luminescence;Luminescent Proteins;Maps;Mass Spectrum Analysis;Measurement;metal complex;Metals;Modeling;Molecular;Molecular Conformation;molecular modeling;nanocluster;nanocomplexes;nanomedicine;Peptides;Photons;Process;Property;Protein Analysis;protein data bank;protein function;protein protein interaction;Proteins;Publications;Pump;Research;Signal Transduction;Spectroscopy, Fourier Transform Infrared;Spectrum Analysis;Structure;Students;temporal measurement;Testing;Time;tool;Transmembrane Transport;undergraduate student;Universities

PROJECT_TITLE: Investigating common luminophore in protein-metal nano-complexes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MGG-X (81)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE (RELEVANCE) The Washington Heights, Inwood Columbia Aging Project is a longitudinal, community-based, multi-ethnic cohort of older adults. To investigate endogenous metabolites related to Alzheimer's disease (AD) and exogenous metabolites related to external exposures associated with AD, we propose a genetically driven, longitudinal analyses of metabolites in this well characterized cohort from existing plasma. This study will provide an opportunity to add deep phenotyping using metabolomics to a community-based, genetically characterized, multi-ethnic cohort that will help clarify the underlying mechanisms linking genetic pathways and antecedent risk factors associated with AD.

PI_NAMEs: MAYEUX, RICHARD P (contact);MILLER, GARY W;VARDARAJAN, BADRI N

PROGRAM_OFFICER_NAME: YAO, ALISON Q

PROJECT_TERMS: African American;African American population;Age;Aging;Alcohols;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease risk;Biochemical;Biological;Biological Assay;biomarker development;Blood;Caribbean Hispanic;cerebrovascular;Chemicals;Clinical Data;Cognitive;cognitive testing;cohort;Cohort Studies;Collection;Communities;Data;Data Set;Dementia;Development;Dietary Practices;Disease;Disease Progression;DNA;Elderly;Environmental Risk Factor;Epidemiology;Equation;Ethnic Origin;Ethnic Population;exome sequencing;follow-up;Framingham Heart Study;functional genomics;gene environment interaction;Genes;Genetic;genetic analysis;Genetic Risk;genetic risk factor;genetic variant;Genome;genome sequencing;genome wide association study;Glycosphingolipids;Goals;Height;Human;Human body;Impaired cognition;in vivo;Individual;informant;Investigation;Life Style;lifestyle factors;Link;longitudinal analysis;longitudinal design;Measures;Mediating;Mediation;Medical;medical examination;Memory;Meta-Analysis;Metabolism;Metabolite Interaction;metabolome;metabolomics;molecular phenotype;multi-ethnic;neuroimaging;Neurologic;Neurologic Examination;Not Hispanic or Latino;older adult;participant interview;Pathway interactions;Phenotype;Physical activity;Physiological;Plasma;polygenic risk score;protective factors;Race;Registries;religious order study;Resources;response;Risk;Risk Factors;Severities;Severity of illness;sex;Sleep;Smoking;Sphingomyelins;standard measure;Telephone Interviews;Testing;therapeutic development;Time;Urban Community;Washington;Wisconsin

PROJECT_TITLE: Epidemiological Integration of Genetic Variants and Metabolomics Profiles in Washington Heights Columbia Aging Project

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-F(56)]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Dementia;Neurodegenerative;Neurosciences

ORG_DEPT: BIOLOGY

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: PROJECT NARRATIVE The Alzheimer's disease (AD) peptide, beta-amyloid, can activate the coagulation system, which can lead to 1) blood clotting and 2) inflammation upon cleavage of a particular protein. We have generated antibodies that can be used to quantitate the level of this protein in human blood as well as prevent cleavage and release of the inflammatory molecule. These antibodies could be beneficial to patients, since they may diagnose AD prior to cognitive symptoms as well as therapeutically lessen inflammation and protect against abnormal blood clotting, both of which are AD pathologies.

PI_NAMEs: NORRIS, ERIN H (contact)

PROJECT_TERMS: Abbreviations;Age;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease diagnostic;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease test;Amyloid beta-Protein;Antibodies;antibody test;Antisense Oligonucleotides;arm;Biological Assay;Blocking Antibodies;Blood;Blood coagulation;Blood Coagulation Factor;Blood Vessels;Bradykinin;Brain;Cerebral hemisphere hemorrhage;Clinical;Coagulation Process;cofactor;Complex;Detection;Diagnostic;Diagnostic tests;effective therapy;Enzyme-Linked Immunosorbent Assay;Factor XI;Factor XIIa;Generations;Goals;Hemorrhage;High-Molecular-Weight Kininogen;Human;in vivo;in vivo evaluation;Individual;Inflammation;Inflammatory;inhibiting antibody;interdisciplinary approach;knock-down;Modeling;Monoclonal Antibodies;mouse model;Mus;Neurobehavioral Manifestations;Neurodegenerative Disorders;neuroinflammation;non-demented;Pathologic;Pathology;Pathway interactions;Patients;Peptides;Persons;Plasma;Plasma Kallikrein;prevent;Prostate-Specific Antigen;protein activation;Proteins;Research;Role;Sampling;Scheme;System;Testing;Therapeutic;Therapeutic Uses;Vascular Diseases;Vascular System

PROJECT_TITLE: Anti-high molecular weight kininogen antibody for Alzheimer's disease diagnosis and therapy


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Cardiovascular;Dementia;Genetics;Heart Disease;Human Genome;Neurodegenerative;Prevention

ORG_CITY: MINNEAPOLIS

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative  This proposed research is expected to not only advance statistical analysis for causal inference to identify novel and putatively causal proteins and metabolites for Alzheimer's disease (AD) and atrial ﬁbrillation (AF), but also contribute valuable computational tools to the elucidation of genetic components of common diseases, thus facilitating their prevention, early diagnosis and therapeutic development.

PI_NAMEs: PAN, WEI  (contact)

PROJECT_TERMS: Accounting;Address;Aging;Alzheimer's Disease;Alzheimer's disease risk;Atrial Fibrillation;Biological;causal variant;Clinical;cohort;Communities;Complex;Computer software;computerized tools;cost effective;Data;Data Analyses;Data Set;diagnostic tool;Disease;Documentation;drug development;Early Diagnosis;Environment;Etiology;Gene Expression;Genes;Genetic;genetic variant;genome wide association study;Genomics;Goals;improved;Individual;Influentials;insight;Intervention;Knowledge;Least-Squares Analysis;Link;Linkage Disequilibrium;Mediating;Mendelian randomization;metabolomics;method development;Methods;Modeling;novel;Phenotype;pleiotropism;practical application;Prevention;programs;Proteins;Proteomics;Public Domains;Publishing;Quantitative Trait Loci;Relaxation;Research;response;Risk Factors;Sampling;secondary analysis;software development;Statistical Computing;Statistical Data Interpretation;Statistical Methods;statistics;Testing;therapeutic development;therapy development;trait;Transcript;transcriptome;transcriptomics;Untranslated RNA;web site;Work;Writing

PROJECT_TITLE: Integrating Alzheimer's disease GWAS with proteomic and metabolomic QTL data

STUDY_SECTION: NAME

STUDY_SECTION_NAME: Neurological, Aging and Musculoskeletal Epidemiology Study Section[NAME]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Nutrition;Prevention;Sleep Research

ORG_CITY: La Jolla

ORG_NAME: SALK INSTITUTE FOR BIOLOGICAL STUDIES

PHR: Sleep and circadian rhythm deteriorate with aging and compromise the function of the brain and  body. This proposal suggests a method for investigating how chronic circadian rhythm  disruption, which is intimately interlinked with cellular metabolism, affects Alzheimer's  disease (AD) pathology. Conversely, optimum eating time will be used a novel intervention to  optimize circadian rhythm and reduce the severity of AD pathology.

PI_NAMEs: MELKANI, GIRISH C.;PANDA, SATCHIDANANDA  (contact)

PROGRAM_OFFICER_NAME: MACKIEWICZ, MIROSLAW

PROJECT_TERMS: Acceleration;Address;Adoption;Affect;Age;age acceleration;age related;age related chronic disease;age related decline;Aging;aging process;Alleles;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease risk;Amyloid beta-42;Animals;Attenuated;Behavior Therapy;Biological Process;Brain;Caloric Restriction;Candidate Disease Gene;Cardiac;Cell Physiology;chaperonin CCT;Chronic;circadian;circadian behavioral rhythms;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;cohort;Competence;Consumption;Coupled;Darkness;Deterioration;differential expression;Disease;disease model;disease phenotype;Drosophila genus;Drosophila melanogaster;Eating;efficacy evaluation;Energy Intake;Environment;Exhibits;experimental study;Eye;feeding;fly;Food;functional decline;gain of function;Gene set enrichment analysis;Genes;Genetic;Genetic Models;Genetic Risk;Geroscience;Harvest;Head;heart function;Hour;Human;improved;in vivo;insight;Intervention;life span;Light;Locomotion;loss of function;Measures;Mediating;Metabolic;Metabolism;Methods;Mitochondria;Modeling;Molecular;Molecular Chaperones;Molecular Profiling;Monitor;Muscle;Muscle function;mutant;Mutation;Nervous System Disorder;neural;Neurons;novel;Onset of illness;Organ;Pathology;Pathway interactions;Pattern;Performance;Peripheral;Phenotype;Production;protective effect;protein folding;repaired;Research;Rest;Risk;Risk Factors;RNA;Role;Series;Severities;Severity of illness;Sleep;Sleep Wake Cycle;tau Proteins;Techniques;Testing;Time;Time-restricted feeding;Tissues;tool;Transcript;transcriptome;transcriptomic profiling;Transgenic Organisms

PROJECT_TITLE: Optimized Circadian Rhythms for the Prevention of Alzheimer's Disease

STUDY_SECTION: CMAD

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: PROJECT NARRATIVE Alzheimer’s disease (AD) is the most common form of dementia and the sixth leading cause of death in the United States. We propose to use the latest single cell proteomics technologies to investigate the dynamics of diverse cell populations in AD models, and to decipher and validate leading targets in dynamic cell-cell interaction and AD pathogenesis using human AD cases, as well as mouse and human organoids models.

PI_NAMEs: PENG, JUNMIN  (contact);ROSSOLL, WILFRIED

PROJECT_TERMS: age related;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Amino Acids;Animal Model;Animals;Astrocytes;Autophagocytosis;Brain;brain tissue;Candidate Disease Gene;Cause of Death;Cell Communication;cell type;Cells;Complex;Data;Data Set;Dementia;Development;Disease;effective therapy;Event;Female;Genes;Genetic study;Genetic Transcription;Genotype;Goals;hTau Mice;Human;human data;In Situ;inducible Cre;Investigation;Knock-in;Knowledge;Label;male;Mass Spectrum Analysis;Measures;Mediating;Microglia;Modeling;Molecular;Molecular Profiling;mouse model;Mouse Protein;multiple omics;Mus;Neuronal Dysfunction;Neurons;novel;novel therapeutic intervention;Organoids;Outcome;Pathogenesis;Pathology;Pathway interactions;Peptide Hydrolases;Physiologic pulse;Physiological;Population;postmitotic;posttranscriptional;protein degradation;Protein Dynamics;protein function;Protein Secretion;Proteins;Proteome;Proteomics;Protocols documentation;RNA;Sampling;secretory protein;sex;Signal Transduction;Specimen;System;Systems Biology;Technology;transcriptome;transcriptomic profiling;transcriptomics;transgene expression;TREM2 gene;Ubiquitin;United States;Validation;Work

PROJECT_TITLE: Dissecting neuron-microglia-astrocyte interaction in AD pathogenesis


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Prevention

PHR: PROJECT NARRATIVE Increasing the function of the proteasome (protein complexes involved in protein turnover) can reduce cognitive deficits associated with aging as well as in various models of Alzheimer’s disease. We now plan to test whether genetic and pharmacologic manipulation of this system can rescue cognitive deficits in mouse models of Alzheimer’s disease, and to examine how proteasome manipulation alters Alzheimer’s disease progression. The ultimate goal of this work is to develop new drugs and interventions aimed at slowing or preventing Alzheimer’s disease progression.

PI_NAMEs: PICKERING, ANDREW MICHAEL (contact)

PROJECT_TERMS: abeta accumulation;Acceleration;Affect;Age;age related;age related decline;Aging;aging brain;Agonist;Alzheimer disease prevention;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease related dementia;Alzheimer's disease risk;American;Amyloid beta-42;Amyloid beta-Protein;Amyloid beta-Protein Precursor;amyloid precursor protein processing;Animal Model;Area;beta secretase;beta-site APP cleaving enzyme 1;Biological Markers;Blood - brain barrier anatomy;Brain;brain tissue;Cell Culture Techniques;Cells;Cognitive;Cognitive deficits;Data;Development;Disease;disease model;Disease Progression;Disease susceptibility;Drosophila genus;Drug Targeting;Excision;experience;fly;functional decline;Functional disorder;gamma secretase;Genetic;genetic manipulation;Goals;Human;human tissue;Impairment;In Vitro;in vivo;Intervention;Intervention Studies;Invertebrates;Investigation;J20 mouse;knock-down;Knock-in Mouse;Lead;Libraries;Link;Modeling;mortality;mouse model;multicatalytic endopeptidase complex;Mus;Mutate;Nerve Degeneration;Neurons;novel;novel therapeutics;Onset of illness;Outcome;overexpression;Pathogenesis;Pathology;Patients;Penetrance;Pharmaceutical Preparations;pharmacologic;Phenotype;Play;Polyubiquitination;preclinical trial;presynaptic;prevent;protective effect;protein complex;protein degradation;Proteins;proteostasis;rational design;Reporting;Research;Research Personnel;Rodent;Role;Severities;Site;Symptoms;Synapses;System;Testing;Therapeutic;therapy development;timeline;Transgenic Mice;Translating;translational potential;treatment strategy;vesicle transport;Work

PROJECT_TITLE: Proteasome dysfunction as a driver of age-associated risk for Alzheimer's disease onset and progression


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE Forty-seven million people suffer from Alzheimer's disease (AD) worldwide, but there is still no adequate treatment for this devastating neurodegenerative illness. Our lab has recently discovered that persons with late-onset AD, the most common form of this disease, express high levels of an enzyme called NAAA, and that inhibiting the activity of this enzyme markedly attenuates neurodegeneration in a mouse model. Here, we propose a series of animal experiments to determine whether NAAA contributes to AD progression, and whether drugs that block NAAA activity might be used to delay this process.

PI_NAMEs: GREEN, KIM ;PIOMELLI, DANIELE  (contact)

PROJECT_TERMS: Acids;Affect;age related;Agonist;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;amidase;Animal Experiments;Animal Model;Anti-Inflammatory Agents;Attenuated;Behavioral;Biological;blood-brain barrier crossing;Brain;Chronic;Cysteine;Disease;Disease Marker;Disease Progression;effective therapy;energy balance;Energy Metabolism;enzyme activity;Enzymes;Excision;experimental study;Functional disorder;Gene Modified;Genetic;Genetic Transcription;Goals;Hydrolase;Immune;Impaired cognition;Inflammation;inhibitor;innovation;Late Onset Alzheimer Disease;Lipid Biochemistry;lipidomics;Lipids;Medical Research;Modeling;Molecular;molecular targeted therapies;Morphology;mouse model;Multiple Sclerosis;Mus;Natural Immunity;Nerve Degeneration;Neurodegenerative Disorders;Neurofibrillary Tangles;Neurons;neuroprotection;novel;Nuclear Receptors;palmidrol;Palmitates;Parkinson Disease;Pathogenesis;Persons;Pharmaceutical Preparations;pharmacologic;Pharmacology;PPAR alpha;Process;protective effect;Research;Role;Senile Plaques;Series;Severities;Signal Transduction;single-cell RNA sequencing;Symptoms;tau Proteins;Testing;therapeutic target;Transcription Coactivator;United States

PROJECT_TITLE: The lipid amidase NAAA as a therapeutic target for Alzheimer's disease

STUDY_SECTION: MNPS

STUDY_SECTION_NAME: Molecular Neuropharmacology and Signaling Study Section[MNPS]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences

ORG_DEPT: NEUROSCIENCES

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative Ageing is a major risk factors for neurodegenerative diseases and is associated with the systemic activation of an inflammatory microglia state. We propose to address the epigenetic mechanisms underlying the enhanced pro-inflammatory activity of microglia in the ageing brain and its contribution to neurodegeneration Our studies will establish a foundation for the development of novel therapeutic approaches against neurodegeneration by targeting epigenetic regulators of inflammation by microglia.

PI_NAMEs: SCHAEFER, ANNE  (contact);TARAKHOVSKY, ALEXANDER

PROJECT_TERMS: Ablation;Acute;Address;Affect;Age;age related;age related changes;age related neurodegeneration;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease model;Amyloid beta-Protein;Animals;Attenuated;Binding;Brain;Brain region;BRD2 gene;Bromodomain;Bromodomains and extra-terminal domain inhibitor;cell type;Cells;Chromatin;Communicable Diseases;cytokine;Data;Development;Disease;Disease Progression;Enhancers;Epigenetic Process;Exposure to;Foundations;Gene Expression;Gene Expression Profiling;Genes;Genetic Transcription;genomic locus;Human;Immune;immune activation;Immunity;imprint;In Vitro;in vivo;Individual;Inflammation;Inflammatory;Inflammatory Response;influenza infection;Life;Link;Macrophage;Mediating;Microglia;Modeling;Monitor;Mus;Natural Immunity;Nature;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;neuroprotection;neurotoxic;novel strategies;novel therapeutic intervention;Onset of illness;Output;pharmacologic;Phenotype;Physiological;Play;Poly I-C;prevent;Process;Production;Proteins;Recording of previous events;response;Risk Factors;Role;Severity of illness;Signal Induction;Signal Transduction;Stimulus;systemic inflammatory response;Testing;Therapeutic;Tissues;Training;Transcriptional Regulation;Up-Regulation

PROJECT_TITLE: Age-dependent activation of microglia inflammatory state and its epigenetic modulation


PHR: Project Narrative Aging is the major risk factor for Alzheimer’s disease (AD) and ~50% of AD risk genes are expressed by microglia, resident immune cells of the central nervous system (CNS). This project will investigate how cellular senescence, which increases with age, affects microglia function and transition to an inflammatory cell type to affect neuroinflammation and neurodegeneration relevant to AD. The success of this project will uncover new mechanisms by which the aging brain influences AD pathogenesis and will likely uncover novel microglia-based mechanisms for therapeutic intervention.

PI_NAMEs: SCHAFER, DOROTHY PATRICIA (contact);ZHANG, HONG

PROJECT_TERMS: Ablation;Acceleration;Acute;Address;Affect;Age;age related neurodegeneration;Aging;aging brain;aging related disease;Alzheimer associated neurodegeneration;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease risk;Amyloid;Amyloid beta-Protein;APP-PS1;astrocyte progenitor;Attenuated;beta-Galactosidase;biological adaptation to stress;Biology;Brain;CDKN2A gene;Cell Aging;Cell Culture Techniques;cell type;Cells;Central Nervous System;Chronic;cytokine;Data;Defect;Deposition;Disease;DNA Damage;Elderly;Exhibits;experimental study;Functional disorder;Genes;Genetic;Genetic Transcription;Goals;Homeostasis;IL8 gene;Image;Immune;Immunofluorescence Immunologic;Impairment;In Vitro;in vivo;in vivo evaluation;Inflammation;Inflammatory;Injury;insight;Interleukin-1 beta;Interleukin-6;Knock-in Mouse;Lasers;Learning;Lentivirus;Ligase;Macrophage;Mediating;Mediator;Memory Loss;Metabolic;Microglia;Morphology;mouse model;Mus;Nerve Degeneration;neural circuit;Neurodegenerative Disorders;neurodegenerative phenotype;Neuroglia;neuroinflammation;neuroprotection;neuroregulation;novel;novel therapeutics;oligodendrocyte progenitor;Oncogenic;Outcome;overexpression;Oxidative Stress;Pathogenesis;Phagocytes;Phagocytosis;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Positioning Attribute;Process;Proliferating;Protein Overexpression;Regulation;response;Risk Factors;risk variant;Role;senescence;senescence associated secretory phenotype;senescent cell;Senile Plaques;senolytics;Signal Transduction;stem cells;Stimulus;success;Synapses;Synaptosomes;tau Proteins;telomere;temporal measurement;Testing;Therapeutic Intervention;therapeutic target;time use;Tissues;tool;transcriptome sequencing;transcriptomics;Translating;two-photon;ubiquitin-protein ligase;uptake;virtual;Work

PROJECT_TITLE: Dissecting the impact of senescence on microglia function and neurodegeneration


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: SEATTLE

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative Alzheimer disease (AD) affects millions of Americans and many more worldwide and is a significant source of disability and a major burden to society. This study aims to investigate the transportation or clearance of potential toxic proteins from the brain to blood via small membrane vesicles and the potential usage of such proteins in blood plasma as AD biomarkers. The study will likely establish the foundation leading to an inexpensive and clinically routine test that improves AD diagnosis accuracy and/or enhances disease progression monitoring, and ultimately may provide critical opportunities for therapeutically addressing the pathology associated with neurodegeneration in AD.

PI_NAMEs: SHI, MIN  (contact)

PROJECT_TERMS: Address;Affect;alpha synuclein;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease pathology;Alzheimer’s disease biomarker;American;Amyloid beta-42;Amyloid beta-Protein;Animal Model;Animals;Biological Markers;biomarker identification;Blood;blood-brain barrier crossing;Body Fluids;Brain;Brain region;candidate marker;Cell model;cell type;Cells;Central Nervous System;Central Nervous System Diseases;Cerebellum;Cerebrospinal Fluid;Cerebrospinal Fluid Proteins;Clinical;Complex;Corpus striatum structure;Data;diagnostic accuracy;Diagnostic Sensitivity;Diagnostic Specificity;disability;Disease;Disease Progression;disorder control;experimental study;extracellular vesicles;Foundations;Future;Hippocampus;Human;human subject;improved;in vivo;Individual;intercellular communication;Investigation;Mediating;Membrane;Methodology;Midbrain structure;Monitor;nanoparticle;nanoscale;Nerve Degeneration;Nervous System;Neural Cell Adhesion Molecule L1;Neurodegenerative Disorders;Neurons;new technology;novel;Parkinson Disease;Pathogenesis;Pathology;Pathway interactions;Patients;Performance;Pilot Projects;Plasma;Play;prion-like;Protein Export Pathway;Protein Isoforms;Proteins;Proteomics;Publications;Quantitative Microscopy;Reporting;Rodent Model;Role;Sampling;Serum;Severity of illness;single molecule;Societies;Sorting;Source;Specificity;Surface;Synaptic Vesicles;tau Proteins;tau-1;Techniques;Technology;Testing;Therapeutic;tool;Transportation;Vesicle;vesicle transport

PROJECT_TITLE: Extracellular vesicle transport of brain-derived proteins to the blood in Alzheimer disease


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biodefense and Related Countermeasures;Brain Disorders;Dementia;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Liver Disease;Neurodegenerative;Neurosciences

PHR: Principal Investigator/Program Director (Last, first, middle): Soto, Claudio / Morales, Rodrigo PROJECT NARRATIVE Recent reports suggest that the protein aggregates (Aβ and Tau) which are the pathognomic features of Alzheimer's disease (AD), can spread following a similar mechanism to the one described for prion proteins. The aim of this project is to identify and characterize Aβ oligomeric aggregates in blood from AD patients, study the contribution of circulating Aβ oligomers to seed amyloid deposition in the brain and investigate whether impairments in peripheral Aβ clearance influence the progression of the pathological abnormalities in the brain. The outcomes obtained from these studies could change the current view about the etiopathogenesis of AD and uncover new therapeutic and diagnostic strategies.

PI_NAMEs: MORALES, RODRIGO ;SOTO, CLAUDIO  (contact)

PROJECT_TERMS: abeta accumulation;Abeta clearance;abeta deposition;abeta oligomer;Acceleration;Acute;Affect;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease model;Alzheimer's disease patient;Amyloid;Amyloid beta-Protein;Amyloid deposition;amyloid pathology;Animal Experiments;Animal Model;Animals;Appearance;Biochemical;Biodistribution;Biological;Biological Assay;Biophysics;Blood;Blood Circulation;Blood specimen;Blood Transfusion;blood-brain barrier crossing;Brain;Cells;cerebral amyloidosis;Cerebrum;Chronic;Circulation;comparison control;Creutzfeldt-Jakob Syndrome;Data;Deposition;Detection;Development;Diagnosis;Diagnostic;diagnostic strategy;Dialysis procedure;Disease;epidemiologic data;Etiology;Excision;experimental study;Frequencies;Goals;Hematological Disease;Homeostasis;Human;Iatrogenesis;Impairment;In Vitro;in vivo;Individual;intravenous injection;Knock-in Mouse;Knowledge;Lesion;Liquid substance;Liver;liver injury;Methodology;misfolded protein;Modeling;Modification;Monitor;monomer;mouse model;novel;novel diagnostics;novel strategies;novel therapeutic intervention;novel therapeutics;Operative Surgical Procedures;Organ;Outcome;particle;Pathogenesis;Pathogenicity;Pathologic;Pathology;Patients;Peptides;Periodicals;Peripheral;pharmacologic;Plasma;Plasmapheresis;Play;prevent;Principal Investigator;prion-like;Prions;Procedures;Process;programs;Property;protein aggregation;protein misfolding;Proteins;PrP;Radiolabeled;Reporting;Role;sample collection;Side;Somatropin;Structure;tau aggregation;tau Proteins;Techniques;Technology;Testing;Therapeutic;Tissues;Transgenic Animals;Transgenic Mice;transgenic model of alzheimer disease;transmission process;treatment strategy;Whole Blood

PROJECT_TITLE: Role of circulating Abeta seeds and peripheral tissue damage in Alzheimer's disease pathogenesis


ORG_CITY: NORTH CHICAGO

ORG_NAME: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI

PHR: The objective of this study is to determine the pathogenic signaling interactions among key neuronal organelles that contribute to AD pathology. Specifically, we will examine functions of the ER, lysosomes, authophagosomes and mitochondria in AD mouse models and human neurons from AD patients to discover how dysfunction in one organelle disrupts the functions of others, leading to pathogenic protein aggregates and synaptic defects. Benefits to public health include the identification of new cellular pathogenic dynamics and development of novel therapeutic strategies to effictively treat AD.

PI_NAMEs: SEKLER, ISRAEL ;STUTZMANN, GRACE E. (contact)

PROJECT_TERMS: abeta accumulation;Abeta clearance;Acceleration;Affect;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid;Amyloid beta-42;Amyloid beta-Protein;amyloid structure;Automobile Driving;Autophagocytosis;Autophagosome;Biochemical;Bioenergetics;Buffers;Calcium;Calcium Signaling;Cell model;Cells;cellular pathology;Clinical Trials;cognitive function;Confocal Microscopy;Coupled;Coupling;Dedications;Defect;Development;Disease;Disease Progression;Dyes;Electrophysiology (science);Elements;Endoplasmic Reticulum;Excision;Feedback;Fibroblasts;fluorescence imaging;Functional disorder;Gene Expression;Goals;Health;Histopathology;Homeostasis;Human;hyperphosphorylated tau;Image;Immunoassay;Impaired cognition;Impairment;Induced Neurons;Inositol;Investments;ITPR1 gene;Link;Lysosome Proton;Lysosomes;Measures;Mediating;Membrane Potentials;Memory impairment;misfolded protein;Mitochondria;mitochondrial dysfunction;mitochondrial membrane;mouse model;Mus;mutant;Neurodegenerative Disorders;Neurofibrillary Tangles;neuron loss;Neurons;novel therapeutic intervention;operation;Organelles;Outcome;Output;Oxidative Stress;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Post-Translational Protein Processing;Process;protein aggregation;Proteins;Proteolysis;Public Health;Regulation;Resolution;Resources;response;Rest;restoration;RNA Splicing;Role;Ryanodine Receptor Calcium Release Channel;Signal Transduction;Site;Source;Synapses;Synaptic Transmission;tau aggregation;tau Proteins;Testing;Therapeutic;therapeutic target;transcription factor;Transcriptional Activation;tripolyphosphate;two photon microscopy

PROJECT_TITLE: Intracellular organelle deficits driving Alzheimer's disease

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Prevention

ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

PHR: PROJECT NARRATIVE Protein phosphorylation plays an important role in the onset and development of Alzheimer’s disease (AD) but the molecular mechanism of AD pathogenesis is not totally clear and phosphorylation has never been used for diagnosis due to many challenges. This NIH R01 project will attempt to uncover the molecular signaling network that drives the AD progression and develop an innovative phosphoprotein biomarker discovery platform from plasma for AD early detection and monitoring.

PI_NAMEs: TAO, W. ANDY (contact)

PROGRAM_OFFICER_NAME: HSIAO, JOHN

PROJECT_TERMS: abeta deposition;Affect;Alzheimer disease detection;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease therapeutic;Alzheimer’s disease biomarker;Amyloid;Amyloid beta-Protein;biomarker discovery;Blood Tests;Cell membrane;Cell Physiology;Cells;Cerebral cortex;Characteristics;Clinical;clinical diagnosis;clinical diagnostics;Cognitive;Complement;Deposition;Detection;Deterioration;Developed Countries;Development;Diagnosis;Diagnostic;Disease;disease diagnosis;Disease Marker;Disease Progression;driving force;early detection biomarkers;Early Diagnosis;early onset;Endosomes;Event;exosome;extracellular vesicles;Fibrin;fighting;Fluorescence;Goals;high throughput screening;hyperphosphorylated tau;improved;In Vitro;Incidence;innovation;insight;Link;liquid biopsy;magnetic beads;Maps;Mass Spectrum Analysis;Measures;Memory;Methods;microvesicles;Molecular;Molecular Disease;Monitor;Neurodegenerative Disorders;novel;novel marker;novel strategies;Onset of illness;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Phosphoproteins;phosphoproteomics;Phosphorylation;Phosphotransferases;Physiological;Plasma;Play;Population;potential biomarker;Proteins;Proteomics;Research;Research Personnel;Resolution;Role;Signal Pathway;Signal Transduction;Signaling Molecule;Source;Symptoms;tau Proteins;tau-protein kinase;United States National Institutes of Health;upstream kinase;Validation

PROJECT_TITLE: Dissecting signaling pathways and seeking EV phosphoproteins as novel biomarkers for Alzheimer's Disease

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: PHILADELPHIA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: NARRATIVE Memory impairment that includes encoding and retrieval is a hallmark symptom of Alzheimer’s disease (AD). Impairment of memory retrieval also occurs during aging in the absence of dementia. One of the earliest signs of pathology associated with AD is found in the locus coeruleus (LC), the largest nucleus that utilizes the combined neuromodulators norepinephrine and dopamine. The LC can also exhibit decline in normal aging. The studies proposed herein will greatly extend our understanding of the neuromodulatory mechanisms engaged by LC-derived dopamine and norepinephrine that underlie hippocampus-dependent memory. They will also examine the ability of drugs that modulate the activity of these neuromodulators to reverse memory deficits in mouse models of AD and in aged mice without dementia, with the goal of identifying novel therapeutics.

PI_NAMEs: THOMAS, STEVEN A (contact)

PROJECT_TERMS: Adrenergic Agents;Adrenergic Receptor;Affect;Age;Aging;Agonist;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Animal Model;Behavioral Paradigm;Brain;Brain Stem;Cell Nucleus;cell type;Cognition;Cognitive;cognitive benefits;Complement;Cyclic AMP;Data;Dementia;Disease;Dopamine;dopaminergic neuron;Dorsal;Drug Modulation;Episodic memory;Exhibits;Functional disorder;Genetic;genetic approach;genetic manipulation;Genomics;Goals;hippocampal pyramidal neuron;Hippocampus;hyperphosphorylated tau;Impaired cognition;Impairment;improved;Incidence;Learning;Levodopa;locus ceruleus structure;Memory;memory encoding;Memory impairment;memory process;memory recall;memory retrieval;Microtubule-Associated Proteins;Modern Medicine;Molecular;mouse model;Mus;Mutant Strains Mice;Neocortex;Neurodegenerative Disorders;Neuromodulator;Neurons;neuropathology;neuroregulation;Norepinephrine;normal aging;novel;novel strategies;novel therapeutics;old mice;older adult;Pathology;Pharmaceutical Preparations;pharmacologic;Phase;Play;Population;Process;receptor;restoration;Retrieval;Risk Factors;Rodent;Role;Serotonin;Short-Term Memory;Signal Transduction;Source;Symptoms;System;tau Proteins;Testing;Training;Ventral Tegmental Area;Visualization;Wild Type Mouse

PROJECT_TITLE: Catecholaminergic Signaling in Normal Cognition, Aging and Models of Alzheimer's Disease