ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Bioengineering;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative Despite the high performance of automated segmentation, substantial proofreading is required to correct reconstruction errors within large-scale connectomic datasets. To enable auto- corrections at scale in existing and emerging large datasets, we propose to develop “Connects- Proof, a scalable automated proofreading framework for connectomics”, that leverages, integrates, and extends software tools initially developed for the cubic millimeter MICrONS dataset: NEURD (short for NEURal Decomposition), an automated error detection and correction framework, and NeuVue, a scalable manual proofreading platform. Enabled by automated proofreading, accurate large-scale connectomes can provide unprecedented insights to understand brain function.

PI_NAMEs: REIMER, JACOB ;RIVLIN, PATRICIA K (contact);WESTER, BROCK A.

PROGRAM_OFFICER_NAME: JOHNSON, KARI ANNE

PROJECT_TERMS: Active Learning;Algorithms;Area;automated segmentation;Axon;Behavior;Binding;Brain;brain volume;Cells;Collaborations;college;Communities;Computers;connectome;connectome data;cost effective;Data;Data Set;deep learning algorithm;Dendrites;density;Detection;Ecosystem;Electron Microscopy;experience;forging;Foundations;Future;Goals;graph neural network;Grouping;Hour;Human;human data;Human Resources;human-in-the-loop;Image;imaging Segmentation;improved;Individual;Ingestion;insight;Interneurons;Intervention;Laboratories;large datasets;Libraries;Machine Learning;Manuals;Maps;Medicine;Methods;microscopic imaging;millimeter;Motivation;multiple datasets;Mus;Nervous System Disorder;Nervous System Trauma;neural;Neurons;open source;Output;Performance;Physics;prevent;programs;reconstruction;Research;Research Personnel;Resolution;Resources;Services;Software Tools;Speed;Suggestion;Synapses;System;Time;tool;training data;Universities;Validation;Visualization;Work;Writing

PROJECT_TITLE: BRAIN CONNECTS: A Scalable Automated Proofreading Framework for Connectomics

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-S (17)]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research

ORG_CITY: Columbus

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PATHOLOGY

ORG_FIPS: US

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE Cancer is an often-deadly disease without universal treatment options, however new discoveries can lead to new cancer treatments to the benefit of all. Progress is dependent on good scientific ideas supported by high- quality novel resources so that investigators can ask and answer critical research questions. The Cooperative Human Tissue Network Midwestern Division (CHTN MWD) will respond to the cancer researchers’ ever-changing challenges by supporting them with custom prepared high quality human tissues and biofluids enriched by innovative clinical data sets.

PI_NAMEs: PARWANI, ANIL V (contact)

PROGRAM_OFFICER_NAME: CHUAQUI, RODRIGO F

PROJECT_TERMS: Accounting;Adult;Age;Basic Science;Benign;biobank;Biocompatible Materials;bioinformatics infrastructure;Biological Markers;Biological Sciences;Body Fluids;cancer care;Cancer Hospital;cancer therapy;Caring;Clinical;Clinical Data;Code;Collection;common rule;Communities;Comprehensive Cancer Center;Computerized Medical Record;Consent;Cooperative Human Tissue Network;Custom;Data;Data Collection;Data Set;Database Management Systems;Databases;Diagnosis;digital;digital imaging;Disease;Elements;Ethnic Origin;experience;Fees;Future;Gender;Geographic Locations;Geography;Growth;Health;Hospitals;Human;human tissue;Immunohistochemistry;improved;Informatics;innovation;Institution;Institutional Review Boards;interest;International;Journals;Knowledge;Laboratories;Link;Liquid substance;Malignant - descriptor;Malignant Neoplasms;Medical;Medical center;Medical Research;meetings;Methods;Microscopy;Molecular;National Cancer Institute;novel;Ohio;Participant;Pathologist;Pathology;Pathology Report;Patients;Pennsylvania;Performance;personalized medicine;Population;preservation;Privacy;programs;prospective;Protocols documentation;Quality Control;Race;recruit;Reporting;Research;Research Personnel;research study;Resolution;Resources;sample collection;Sampling;Science;Scientific Advances and Accomplishments;Services;Shipping;Site;Testing;Tissue Microarray;Tissue Procurements;Tissues;translational cancer research;Translational Research;translational scientist;tumor;Universities;University Hospitals;waiver

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-K (J1)]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Pediatric

ORG_CITY: NEWARK

ORG_DEPT: PSYCHOLOGY

ORG_NAME: RUTGERS THE STATE UNIV OF NJ NEWARK

ORG_STATE: NJ

PHR: Research Narrative The current study aims to characterize the emotional input that three samples of typically developing infants receive over the first year and a half of life—a critical time period for learning to identify and respond to emotion information. By documenting infants’ natural exposure to emotion information, we can build a better understanding of how infants develop emotion categories, how they learn to use emotion information to guide action and build expectations about social interactions, and how specific experiences or individual differences shape development in these domains.

PI_NAMEs: LOBUE, VANESSA  (contact)

PROGRAM_OFFICER_NAME: ESPOSITO, LAYLA E

PROJECT_TITLE: Describing the emotional environment of the infant from 6 to 17 months

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: Project Narrative The human intestinal flora is a complex environment where bacterial and fungal organisms co-exist in the gut. While the microbiome can profoundly influence host physiology, specific fungal-bacterial transkingdom interactions remain poorly characterized. The proposed research will analyze interactions between these organisms and their specific influence on immunity and mycobiota.

PI_NAMEs: GUO, CHUN-JUN ;ILIEV, ILIYAN DIMITROV (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Affect;anti-fungal agents;antigen-specific T cells;Area;Bacteria;Binding;Candida;Candida albicans;Chemicals;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Collection;colonization resistance;commensal bacteria;Communities;Complex;computerized tools;CRISPR/Cas technology;Cues;Data;design;Development;Disease;Ecosystem;Environment;Feces;Fungal Antigens;fungal microbiota;fungus;Gastrointestinal tract structure;Gene Cluster;Gene Transfer;Genes;Genetic;genetic manipulation;Germ-Free;Gnotobiotic;Growth;gut bacteria;gut colonization;gut microbiota;high throughput screening;Homeostasis;host colonization;Human;human microbiota;Immune;Immune response;Immune system;Immunity;immunogenic;immunoregulation;In Vitro;in vivo;in vivo Model;Inflammation;interest;Intestines;Investigation;Laboratories;Libraries;Light;Literature;Mediating;member;Metabolic Pathway;metabolomics;Metagenomics;Methodology;Methods;Microbe;microbial;Microbial Biofilms;microbial community;microbial composition;microbiome;microbiota;microbiota metabolites;Modeling;Molecular;mouse model;Mus;mutant;mycobiome;Mycoses;Nature;novel;Organism;pathogen;pathogenic fungus;Pathway interactions;Phylogenetic Analysis;Physiology;Play;Production;Property;Publishing;rational design;Research;Role;rRNA Genes;screening;Shapes;Side;small molecule;Structure;System;Testing;tool;Virus;Work

PROJECT_TITLE: Investigation of gut microbiota metabolite-mediated transkingdom interactions with fungi

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 DCAI-F (02)]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Aging;Bioengineering;Biotechnology;Dental, Oral, and Craniofacial Disease;Infectious Diseases;Regenerative Medicine

ORG_CITY: IOWA CITY

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE (RELEVANCE) Almost 50% of American adults over 30 years old have periodontitis, which represents around 65 million people, 9% of them have severe periodontitis, and the prevalence increases gradually with age. Current treatments for periodontitis, including the standard scaling and root planing combined with systemic or local administration of antibiotics or antiresorptive bisphosphonate, do not effectively address safety concerns or adequately prevent periodontal bone loss. Instead of relying on exogenous cells, proteins, or antibiotics, our study develops an innovative biomaterials-based strategy with strong anti-inflammatory, anti-bacterial, and bone-forming abilities to prevent periodontitis-induced bone loss and improve periodontal bone regeneration by enhancing our body’s innate healing capacity.

PI_NAMEs: SUN, HONGLI  (contact)

PROGRAM_OFFICER_NAME: LOPEZ, ORLANDO

PROJECT_TERMS: Address;Adult;Age;Aging;alpha ketoglutarate;Alveolar Bone Loss;American;anti aging;Anti-Bacterial Agents;Anti-Inflammatory Agents;Antibiotics;antimicrobial;Attenuated;Bacteria;Bacterial Antibiotic Resistance;Bacterial Infections;Basic Science;Biocompatible Materials;Bioglass;Biological;bisphosphonate;bone;bone loss;Bone Regeneration;Bone structure;Cell Culture Techniques;Cells;Chitosan;Chronic;Citric Acid Cycle;Clinical Research;clinically relevant;Collaborations;cytokine;Data;Defect;Dental Implants;Development;differentiation in vitro;effective therapy;Effectiveness;effectiveness evaluation;Failure;Future;Gene Expression;Genes;Goals;Growth;healing;Hydrogels;improved;In Vitro;Inflammation;Inflammatory;Injectable;innovation;Iowa;Ligature;Macrophage;Mediating;Mediator;Methods;microbial;microCT;mineralization;mouse model;novel;novel strategies;novel therapeutic intervention;old mice;Osseointegration;osteoclastogenesis;Osteogenesis;osteogenic;Outcome;pathogenic bacteria;Patients;Periodontitis;Permeability;Persons;Pharmaceutical Preparations;Pilot Projects;Polymers;Prevalence;prevent;Property;Proteins;repaired;Risk;Safety;scaling and root planing;stem cells;Techniques;Therapeutic;Time;Tissue Engineering;Tissues;Tooth Loss;translational potential;Treatment Effectiveness;Universities;vanillin

PROJECT_TITLE: Novel Injectable Biomaterials for Periodontitis

STUDY_SECTION: ODCS

STUDY_SECTION_NAME: Oral, Dental and Craniofacial Sciences Study Section[ODCS]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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;Clinical Research;Dementia;Frontotemporal Dementia (FTD);Machine Learning and Artificial Intelligence;Neurodegenerative;Neurosciences

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Frontotemporal dementia (FTD) spectrum disorders represent one of the most common causes of dementia in younger individuals but can be challenging to diagnose, resulting in high social and economic burden. FTD often causes changes to a patient’s speech, which makes speech an ideal target for a digital tool to aid the diagnosis of FTD. In this proposal, we outline a project to develop a digital technology that will use speech recordings from a self-administered speech exam and provide predictions for abnormal speech characteristics and FTD subtype using machine learning.

PI_NAMEs: BOTHA, HUGO  (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: accurate diagnosis;Address;Adult;Alzheimer disease detection;Alzheimer's disease related dementia;Area;Articulation;automated assessment;Automation;Caring;Cause of Death;Cellular Phone;Characteristics;Classification;Clinic;Clinical;clinical practice;Cognitive;cohort;Data;Data Set;deep learning;deep learning model;Dementia;Detection;Development;Diagnosis;digital technology;digital tool;Dimensions;disability;Disease;Distributed Systems;Economic Burden;Equipment;Failure;falls;feature detection;feature extraction;Foundations;frontotemporal degeneration;Frontotemporal Dementia;Funding;Future;Goals;Head;improved;Individual;innovation;insight;interest;Label;Language;large datasets;Linguistics;longitudinal analysis;Machine Learning;Modeling;National Institute on Aging;Neighborhoods;Online Systems;Pathologist;Patient Care;Patients;Performance;performance tests;predictive modeling;Prevalence;prospective;Prospective Studies;Provider;Quality of Care;recruit;Research;Research Proposals;Research Support;Sample Size;Sampling;Self Administration;self supervised learning;Signal Transduction;social;Specialist;Speech;Speech Disorders;Speech Pathologist;Tablets;Technology;Testing;tool;Training;United States;Update;Validation;validation studies;Voice;Work

PROJECT_TITLE: Automated speech assessment for diagnosis of FTD spectrum disorders

STUDY_SECTION: MFSR

STUDY_SECTION_NAME: Motor Function, Speech and Rehabilitation Study Section[MFSR]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Aging;Diabetes;Obesity;Physical Injury - Accidents and Adverse Effects

ORG_CITY: TROY

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: RENSSELAER POLYTECHNIC INSTITUTE

PHR: Project Narrative Non-enzymatic glycation (NEG) of bone, a modification of matrix by sugars, is associated with type 2 diabetes (T2D) and linked to bone fragility fractures. This project will establish Carboxymethyl-lysine (CML), a product of NEG, as a new biomarker of T2D fracture and determine how the oxidation and glycation processes, associated with diabetes under obese and non-obese conditions, impact accumulation of CML and other AGEs and enhance bone fragility. The results will open new strategies to diagnose, treat and mitigate T2D and fragility fractures.

PI_NAMEs: VASHISHTH, DEEPAK  (contact)

PROGRAM_OFFICER_NAME: JOSEPH, LYNDON

PROJECT_TERMS: Adult;Advanced Glycosylation End Products;Affect;Age;Aging;Assessment tool;Biochemical;Biological Assay;Biological Markers;Body Composition;bone;Bone Density;bone fragility;bone loss;Bone Matrix;bone quality;Bone Tissue;bone toughness;Cadaver;Calcium ion;Charge;Clinical;Collagen;comparison control;cortical bone;Data;Data Analyses;Data Set;Diabetes Mellitus;diabetic;Diagnosis;Disease;Dominant-Negative Mutation;Etiology;Exhibits;Femur;First lumbar vertebra;Fracture;fracture risk;fragility fracture;Glucose;glycation;Glyoxal;Goals;Growth;Health;Health Care Costs;health data;High Fat Diet;Hip Fractures;Human;Hydroxyapatites;Hyperglycemia;Impairment;In Vitro;in vivo;in vivo Model;Individual;Insulin-Like-Growth Factor I Receptor;Length;Link;Measurement;Measures;mechanical properties;Mechanics;microCT;mineralization;Minerals;MM form creatine kinase;Modification;Molecular;mouse model;Mus;muscle engineering;N(6)-carboxymethyllysine;Natural Products;Non obese;Non-Insulin-Dependent Diabetes Mellitus;Obesity;oxidation;Oxidative Stress;Patients;pentosidine;Persons;Post-Translational Protein Processing;Predisposition;Process;promoter;Property;Proteins;Quality of life;Reaction;Ribose;Risk;Roentgen Rays;Role;Serum;skeletal;Skin;Specimen;Spinal Fractures;spine bone structure;substantia spongiosa;sugar;Techniques;Testing;tibia;Time;Tissues;tool

PROJECT_TITLE: Effects of Advanced Glycation Endproducts on Type 2 Diabetes and Fragility Fractures


NIH_SPENDING_CATS: Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE The goals of this application are highly relevant to furthering research in cancer and other diseases and in engaging and educating patients and the public regarding research opportunities in biospecimens donation. By providing high quality well-annotated human tissue biospecimens in a cost-effective manner, CHTN-VUMC will facilitate research that will increase our understanding of human diseases and may eventually have a significant impact on public health and the care of the individual patient.

PI_NAMEs: WASHINGTON, MARY KAY (contact)

PROJECT_TERMS: Academic Medical Centers;Achievement;Adherence;Adult;Advocacy;Awareness;Basic Science;biobank;Biological;Biomedical Research;Blood;Businesses;Caring;Cells;Clinical;Collection;Communication;Communities;Complex;Computer software;Confidentiality of Patient Information;Cooperative Human Tissue Network;cost effective;design;Development;Disease;Disparity population;Education;Ensure;Ethics;experience;Feedback;Fresh Tissue;Funding;Goals;Human;human disease;human subject protection;human tissue;improved;individual patient;Informatics;Infrastructure;innovation;International;Leadership;Malignant Neoplasms;Marketing;member;Modeling;Modernization;neoplastic;network informatics;novel;operation;patient engagement;Patients;Performance;Play;Process;Productivity;programs;prospective;Public Health;Qualifying;Quality Control;Rare Lesion;repository;Research;Research Personnel;response;Role;satisfaction;Science;Security;Services;Site;social media;Societies;Solid;Source;Specimen;Suspensions;System;Technology;Tennessee;Thinness;Tissues;Translational Research;Tube;tumor progression;Tumor-Infiltrating Lymphocytes;web services

PROJECT_TITLE: Tennessee Valley Cooperative Human Tissue Network


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;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Despite recent evidence of the role of grit (i.e., persistence of effort, perseverance) in cognitive resilience in aging, causal evidence is nonexistent. By combining brain imaging with transcranial magnetic stimulation, this project will determine if modulation of neural circuits via stimulation leads to improved grit and memory in healthy aging and preclinical Alzheimer’s disease.

PI_NAMEs: TOUROUTOGLOU, ALEXANDRA  (contact)

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: abeta accumulation;Adult;Age-associated memory impairment;Aging;Alzheimer's Disease;Amyloid;Anterior;Atrophic;Attenuated;behavior test;Biological Markers;Biology;Brain;Brain imaging;Cognitive;cognitive ability;Cognitive aging;cognitive function;cognitive task;Complex;design;discounting;Elderly;executive function;Exhibits;Feeling;Functional Magnetic Resonance Imaging;goal oriented behavior;Goals;healthy aging;Impaired cognition;improved;Individual;innovation;Intervention;Laboratories;Link;Magnetic Resonance Imaging;Measures;Mediating;Memory;Memory Loss;Modeling;Motivation;neural;neural circuit;neural model;Neurobiology;neuromechanism;neuropathology;normal aging;novel;older adult;Outcomes Research;peer;Performance;Persons;pre-clinical;preservation;recruit;repetitive transcranial magnetic stimulation;Reporting;Research;resilience;resilience in aging;response;Risk;Role;Structure;success;Testing;therapy development;Transcranial magnetic stimulation;willingness

PROJECT_TITLE: Grit against cognitive decline in aging and preclinical Alzheimer Disease

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


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;Neurodegenerative;Neurosciences;Nutrition

ORG_CITY: PHILADELPHIA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Ketone supplements and ketogenic diets have the potential to bypass deficits in brain glucose metabolism that occur in Alzheimer’s disease. This proposal will develop and validate noninvasive imaging biomarkers of glucose and ketone metabolism using mouse models that recapitulate human AD. Results from this work will provide an improved mechanistic understanding of the role of lipids and ketone metabolism in AD and lead to clinically translatable biomarkers for better diagnosis and management of deficits in brain metabolism that occur in patients with AD.

PI_NAMEs: REDDY, RAVINDER  (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Accounting;Acetoacetates;Acetone;Address;Affect;aging population;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Animals;Base Ratios;Biological Markers;Brain;brain metabolism;Bypass;Catabolism;Cause of Death;Cell Respiration;Cerebrum;Clinical;Clinical Research;clinical translation;Data;Dementia;Demyelinations;Deuterium;Development;Diagnosis;Disease;Disease Progression;fatty acid oxidation;Glucose;glucose metabolism;Glycolysis;Goals;Homeostasis;Human;imaging biomarker;imaging modality;improved;indexing;Infusion procedures;innovation;insight;ketogenic diet;Ketone Bodies;Ketones;Ketosis;Knock-in;Knock-in Mouse;Label;lipid metabolism;Lipids;Literature;Longitudinal Studies;macromolecule;Magnetic Resonance;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Maps;Measures;medial temporal lobe;Membrane;Metabolic;metabolic rate;Metabolism;Methods;Mitochondria;mouse model;Mus;Myelin;Myelin Basic Proteins;Nature;Nerve Degeneration;NMR Spectroscopy;non-invasive imaging;novel;Nuclear;Onset of illness;Organ;oxidation;Oxidative Phosphorylation;Patient Care;Persons;Protons;Relaxation;Reproducibility;Role;Scanning;Sensitivity and Specificity;Structure;Supplementation;tau Proteins;Testing;Therapeutic;Time;tool;Translating;Validation;Water;Wild Type Mouse;Work

PROJECT_TITLE: Novel Imaging Biomarkers of Lipid and Ketone Metabolism in Alzheimer's Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MCST-Q (81)]


ADMINISTERING_IC: DK

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Kidney Disease;Racial and Ethnic Minority Health Research

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Nearly all cases of COVID-19-associated nephropathy (COVAN) occur in persons with high-risk apolipoprotein L1 (APOL1) genotype, resulting in significant morbidity and mortality and a disproportionate burden of kidney disease on persons of West African descent. This study aims to identify host factors that regulate APOL1 and immune-glomerular interactions in COVAN, providing novel biomarkers and therapeutic targets. Improved understanding of the host factors that effect COVAN penetrance and development of targeted therapeutics are critical to mitigating the racial disparities caused by COVAN in COVID-19 related health outcomes and other forms of APOL1 nephropathy.

PI_NAMEs: NYSTROM, SARAH  (contact)

PROGRAM_OFFICER_NAME: RANKIN, TRACY L

PROJECT_TERMS: 2019-nCoV;Acute Renal Failure with Renal Papillary Necrosis;African American;African American population;African ancestry;Aftercare;Apolipoproteins;Automobile Driving;Basic Science;Biological;Biopsy;Black race;career;career development;Cell Compartmentation;cell type;Cell-Mediated Cytolysis;Cells;chemokine;Chronic;Clinical;Code;comparison control;Complement;COVID-19;COVID-19 disparity;COVID-19 impact;COVID-19 pathogenesis;COVID-19 patient;COVID-19 treatment;cytokine;cytotoxicity;Data;Development;Diagnosis;differential expression;Disease;disparity reduction;dosage;Dose;End stage renal failure;Event;experience;Feedback;Focal and Segmental Glomerulosclerosis;Gene Expression;Genes;Genetic;Genotype;glomerulosclerosis;Goals;Health;high risk;Hispanic ancestry;Human;human induced pluripotent stem cells;human tissue;Immune;immune cell infiltrate;Immune response;Immunologic Factors;Immunology;improved;In Vitro;Incubated;Individual;Infection;Inflammatory;Injury;Institution;Integration Host Factors;Interferons;Kidney;kidney biopsy;kidney cell;Kidney Diseases;Kidney Failure;kidney infection;Knowledge;Lead;Ligands;Measurement;Mediating;Mentors;Mentorship;Messenger RNA;Molecular;Morbidity - disease rate;mortality;new therapeutic target;novel marker;Organoids;Outcome;Outcome Measure;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Penetrance;Peripheral Blood Mononuclear Cell;Persons;Physicians;podocyte;Population;post SARS-CoV-2 infection;prevent;primary outcome;Proteins;Proteinuria;Publishing;racial disparity;receptor;Research;response;RNA;Role;SARS-CoV-2 exposure;SARS-CoV-2 infection;Scientist;Signal Transduction;single-cell RNA sequencing;skill acquisition;Stem Cell Research;targeted treatment;Testing;Training;training opportunity;transcriptome;transcriptomics;Transgenic Mice;Translational Research;treatment response;Up-Regulation;Variant;Viral;virology;Virus Diseases

PROJECT_TITLE: Identification of Host-Specific Determinants of APOL1-associated COVAN

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Fellowships in Kidney, Urology, and Hematology[DDK-G]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Contraception/Reproduction;Genetics

ORG_CITY: EAST LANSING

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: PROJECT NARRATIVE Germ cell development requires properly generated piRNAs to maintain germline DNA integrity, the failure of which will impair male fertility. This project aims to unveil how the piRNA processing machinery is constructed in male germ cells, thus critically informing the mechanistic causes of male infertility for targeted therapies. Findings may also lead to a novel strategy for developing non-hormonal male contraceptives.

PI_NAMEs: WANG, YUAN  (contact)

PROGRAM_OFFICER_NAME: KENT, TRAVIS JOHN

PROJECT_TERMS: Adult;Anabolism;Antibodies;Biogenesis;C-terminal;Cementation;Communication;Cytoplasm;Cytoplasmic Granules;Defense Mechanisms;Development;DNA;DNA Transposable Elements;Doxycycline;Electrons;Elements;Embryo;Exclusion;Failure;Family member;Generations;genome integrity;Genomics;Germ Cells;Germ Lines;Gonadal structure;Immunoprecipitation;Impairment;Knowledge;Lead;Male Contraceptive Agents;male fertility;Male Infertility;Mediating;Membrane;Mitochondria;Monitor;mouse model;Mus;mutant;Mutant Strains Mice;Neonatal;new therapeutic target;novel;novel strategies;Outer Mitochondrial Membrane;Peptides;Pilot Projects;piRNA;postnatal;Process;Proteins;recruit;Repression;Ribonucleoproteins;RNA;RNA-Binding Proteins;Role;Signal Transduction;Somatic Cell;Spermatocytes;Spermatogenesis;Spermatogonia;targeted treatment;Tertiary Protein Structure;Testing;Testis;transcriptome sequencing;Transmission Electron Microscopy;Untranslated RNA;vector;vector control;Virus;Withdrawal

PROJECT_TITLE: Critical protein interactions for piRNA biogenesis

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Reproduction, Andrology, and Gynecology Study Section[CHHD-R]


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

PHR: PROJECT NARRATIVE  Alzheimer’s disease (AD) is the most common form of dementia in older adults, but the contribution of the peripheral immune cells in AD pathology is yet to be fully elucidated. This is partly due to the lack of an effective and reliable model to capture the complex interactions between the various human cellular components of the brain and the peripheral immune cells. Drawing upon our considerable experience in AD biology, 3D modeling of AD in a dish, microfluidic systems, cellular engineering, and bioinformatics, we propose to study the pathogenic roles of CD8+ T cells in AD using our human cellular models and AD-like transgenic mouse models to gain a deeper understanding of CD8+ T cells biology and their disease-modifying role in AD.

PI_NAMEs: JORFI, MEHDI ;KIM, DOO YEON  (contact);PARK, JOSEPH ;TANZI, RUDOLPH EMILE

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: 3-Dimensional;Address;age related;aging population;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer's neuropathogenesis;Antigen Presentation;apolipoprotein E-4;Astrocytes;Automobile Driving;Bioinformatics;Biological Markers;Biology;Brain;brain cell;brain parenchyma;CD8-Positive T-Lymphocytes;Cell Culture Techniques;Cell Death;Cell model;Cell Nucleus;Cells;Cellular biology;cellular engineering;chemokine;chemokine receptor;Clonal Expansion;comparison control;Complex;CXCR3 gene;Data;Dementia;Detergents;Disease;disease model;disease-in-a-dish;Environment;experience;Gene Expression Profile;Genetic;genetic variant;glial activation;Gliosis;Goals;Human;Human Genetics;Immune;Impaired cognition;Infiltration;insight;Interferons;Intervention;knock-down;Knowledge;Ligands;Mediating;Microfluidics;Microglia;mild cognitive impairment;Modeling;Molecular;Molecular Target;monocyte;mouse model;Mus;Nerve Degeneration;neural;Neuroglia;Neuroimmune;neuroinflammation;neuron loss;Neurons;novel;older adult;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway interactions;Peripheral;pharmacologic;Play;prevent;receptor;recruit;Reporting;Role;Signal Pathway;Signal Transduction;Silver Staining;single-cell RNA sequencing;System;T cell infiltration;T-Cell Activation;T-Lymphocyte;tau Proteins;Testing;Therapeutic;therapeutic target;three-dimensional modeling;Transgenic Mice;TREM2 gene

PROJECT_TITLE: Studying the pathogenic roles of human CD8+ T cells in Alzheimer's disease using a 3D human Peripheral immune Chip.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 AN-Z (55)]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Bioengineering;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Hematology;Infectious Diseases;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Sepsis

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Because hospitalized patients with cancer face unacceptable morbidity and mortality from sepsis (a life- threatening dysregulated response to infection), there is urgent need for interventions to identify oncologic sepsis early and enable timelier appropriate treatments. However, incumbent electronic health record-based sepsis prediction tools – linked to improved mortality in other populations – have failed to deliver on their promise in oncology because of design and implementation limitations. This project aims to advance the simultaneous and iterative development of a machine learning tool to predict oncologic sepsis alongside the user-centered design of implementation strategies to improve sepsis care and outcomes for hospitalized patients with cancer.

PI_NAMEs: LYONS, PATRICK G (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Address;Adoption;Algorithms;Antibiotics;antimicrobial;Architecture;Area;Awareness;Blood Tests;cancer care;Cancer Control;cancer therapy;care delivery;career development;Caring;Cessation of life;Clinical;Clinical Trials;cohort;Critical Care;Data;Debility;design;Development;Development Plans;digital;Discrimination;Division of Cancer Control and Population Sciences;Doctor of Philosophy;Dose;Early identification;Early treatment;Electronic Health Record;Ensure;Environment;Epidemiology;evidence base;experience;Face;Failure;Fatigue;Future;Goals;gradient boosting;Health;health care delivery;hospital readmission;Hospitalization;Hospitals;human centered design;implementation barriers;implementation research;implementation science;implementation strategy;implementation tool;improved;improved outcome;Infection;Informatics;information display;innovation;insight;International;Intervention;iterative design;K-Series Research Career Programs;Knowledge;Leadership;Life;Link;Liquid substance;Machine Learning;Malignant Neoplasms;Mentors;Methods;Modeling;Morbidity - disease rate;mortality;multidisciplinary;Oncologist;Oncology;Oregon;Outcome;Patient Care;Patient-Focused Outcomes;Patients;personalized approach;personalized care;Physicians;pilot trial;Population;Positioning Attribute;pragmatic implementation;predictive modeling;predictive tools;Process;prototype;Receiver Operating Characteristics;recurrent neural network;Research;Research Personnel;response;Science;Scientist;Sepsis;skills;Stem cell transplant;success;Survivors;System;Technology;Testing;tool;Training;transfer learning;Translations;Trees;Universities;usability;user centered design;Work

PROJECT_TITLE: SPOT-IT: Sepsis Prediction in Oncology Through Implementation Science and Technology

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Pediatric;Prevention

ORG_CITY: UNIVERSITY

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF MISSISSIPPI

ORG_STATE: MS

PHR: Narrative Poor science achievement in childhood negatively impacts adult health, due to poor scientific literacy and reasoning. LEARN Science – Library Efforts to Advance Reading and Nutrition Science – is an informal life science and reading program through a nutrition science lens to improve science knowledge and science identity among children in kindergarten through second grade (K-2) in Mississippi using public libraries. Informal science education through a nutrition science lens leverages an opportunity for not only improved science achievement, but also for improved health of children – now and in the future.

PI_NAMEs: HOLBEN, DAVID H (contact)

PROGRAM_OFFICER_NAME: FAUPEL-BADGER, JESSICA

PROJECT_TERMS: Academy;Achievement;Adult;Advocate;Age;Biological Sciences;Books;career;Centers for Disease Control and Prevention (U.S.);Child;Child Health;Childhood;Chronic Disease;Communities;Curiosities;Development;disorder prevention;economic disparity;Economics;Education;Employment Opportunities;empowerment;Family;fictional works;Food;food resource;food science;Future;Goals;Health;health disparity;Health education;Health Promotion and Education;Home;improved;Inequity;kindergarten;Knowledge;Learning;Length;lens;Libraries;Library Science;Limited English Proficiency;literacy;materials science;member;Mentors;Mississippi;Modeling;Natural Resources;Next Generation Science Standards;nutrition;nutrition education;Nutritional Science;peer;Persons;Professional Practice;Program Development;programs;racial diversity;Reading;Research Personnel;Resources;Role;Science;science education;Science, Technology, Engineering and Mathematics;scientific literacy;Scientist;second grade;Self Efficacy;social;Spanish;STEM career;System;Terminology;third grade;tool;Translating;United States National Institutes of Health;Youth

PROJECT_TITLE: LEARN Science: A K-2 Life Science and Reading Program in Public Libraries to Improve Science Achievement through Storytelling

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDB-L (55)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Asthma;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative: Asthma health disparities require multi-level solutions that link clinical care to where children learn, live and play. My career plan is designed to build the necessary skills to test these types of interventions. The specific research in this proposal uses a range of methods to develop and pilot test the implementation of undesignated or stock inhaler health policy as a school-based asthma intervention.

PI_NAMEs: PAPPALARDO, ANDREA ARLENE (contact)

PROGRAM_OFFICER_NAME: MINTZER, KEITH A

PROJECT_TERMS: 911 call;acceptability and feasibility;Address;Advocacy;Affect;American Lung Association;Area;Asthma;asthma inhaler;Biostatistics Core;Black race;care delivery;career;career development;Career Mobility;Caring;Chicago;Child;Childhood;Childhood Asthma;Chronic;Clinical and Translational Science Awards;clinical care;clinical trial implementation;Communities;community engaged research;community setting;County;Data;design;Development Plans;dissemination science;Education;Effectiveness;effectiveness outcome;Elements;Emergency Situation;Environment;experience;Exploration, Preparation, Implementation, and Sustainment;flexibility;Funding;Future;Goals;Growth;Health;health administration;health care service utilization;Health Disparities Research;health disparity;health equity;Health Policy;Health Sciences;Health system;Healthcare;High Prevalence;human centered design;Illinois;implementation barriers;implementation facilitators;implementation framework;implementation intervention;implementation outcomes;implementation science;implementation strategy;implementation trial;improved;Inhalators;Intervention;Intervention Trial;Latinx;Lead;Learning;Link;Master of Public Health;Measures;Medicine;Mentored Clinical Scientist Development Program;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Methodology;Methods;Morbidity - disease rate;mortality;Organization and Administration;Organizational Change;Outcome;pediatric department;Pharmaceutical Preparations;Pharmacy facility;pilot test;Play;Policies;population health;Preparation;Process Assessment;programs;Public Health Schools;Public Policy;Publications;Randomized;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Records;Reduce health disparities;Research;research and development;Research Personnel;Resources;Risk;Role;Rural;scale up;school district;School Nursing;Schools;Scientist;Seasons;Secure;Services;skills;Statutes and Laws;suburb;sustainability framework;Symptoms;Testing;Time;Training;trial design;Universities;uptake;Work

PROJECT_TITLE: Policy to Practice: An Implementation Science-Based Approach to Stock Inhalers in Schools

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR (JA)]


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;Microbiome;Neurodegenerative;Neurosciences;Nutrition;Prevention

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Metabolic dysregulation has been implicated in dementia; however, our understanding of metabolic pathways underlying cognitive health is still inadequate. This application aims to systematically investigate brain metabolomic profiles associated with cognitive decline and dementia, by examining approximately 1,800 metabolites in postmortem brain tissue, leveraging data and biospecimens from 1,200 deceased participants in two community-based aging cohorts. Findings from this research may provide critical evidence to fill in the current knowledge gap and to inform the development of novel interventions for the prevention and treatment of dementia.

PI_NAMEs: LI, JUN  (contact)

PROGRAM_OFFICER_NAME: ANDERSON, DALLAS

PROJECT_TERMS: Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Area;Autopsy;Biochemical;Bioenergetics;Brain;brain control;brain tissue;Cerebrum;Cholesterol Homeostasis;Clinical;Cognition;Cognitive;cohort;Communities;Complex;DASH diet;Data;Dementia;dementia risk;Development;Diabetes Mellitus;Diet;Dietary Intervention;Dietary Practices;Energy Metabolism;Etiology;experience;Fatty Acids;Genetic;genome wide association study;genomic data;Genomics;Genotype;Glucose;glucose metabolism;Goals;good diet;gut microbiome;Health;Impaired cognition;Individual;Inflammation;Inflammation Mediators;insulin signaling;Intervention;Knowledge;lipid mediator;Lipids;Longitudinal cohort;machine learning method;Mediating;Mediterranean Diet;Memory;Mendelian randomization;Metabolic;Metabolic Pathway;Metabolism;metabolome;metabolomics;Methods;mild cognitive impairment;Molecular;Nerve Degeneration;neurochemistry;neuropathology;novel;novel strategies;Organ;Outcome;Participant;Pathway interactions;Phenotype;Prefrontal Cortex;prevent;Prevention;Preventive;preventive intervention;Regulation;religious order study;Research;Research Personnel;Research Support;resilience;Resources;Role;Sample Size;Signal Transduction;small molecule;Technology;Testing;Therapeutic Intervention;Work

PROJECT_TITLE: Identification of brain metabolomic profiles associated with dementia


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Neurosciences;Rehabilitation

ORG_CITY: ANN ARBOR

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE Anxiety disorder prevalence climbs during young adulthood, a time when neural circuits involved in emotion regulation undergo significant maturation. This innovative project will identify 1) the ability of young adults with anxiety to self-modulate brain function in a region specific to healthy emotion regulation using real-time functional magnetic resonance imaging neurofeedback and 2) the potential impact of neuromodulation on improved emotion regulation ability and anxiety reduction. Findings from this project will lay the groundwork to test if psychotherapy outcomes can be enhanced using neurofeedback to stop anxiety early.

PI_NAMEs: RUSSMAN BLOCK, STEFANIE RAE (contact)

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TERMS: Adult;Affect;Affective;affective neuroscience;Age;Amygdaloid structure;analog;Anxiety;Anxiety Disorders;anxiety management;anxiety reduction;anxiety symptoms;anxiety treatment;blind;Brain;career;Categories;Characteristics;Clinical;clinical anxiety;clinical translation;cognitive enhancement;cognitive reappraisal;Cognitive Therapy;Control Groups;Data;design;Development;Diagnostic;Disease remission;Educational process of instructing;Effectiveness;efficacious treatment;emotion dysregulation;emotion regulation;Emotional;Ensure;Evaluation;Evidence based treatment;Extramural Activities;Feedback;follow-up;Foundations;Functional Magnetic Resonance Imaging;Funding;Future;Goals;Grant;Image;improved;Individual;innovation;Intervention;Investigational Therapies;K-Series Research Career Programs;Left;Life;Link;Manikins;Measures;Mediating;Mental Depression;Mental Health;Mentors;Meta-Analysis;Methods;negative affect;neural;neural circuit;neurofeedback;neuroimaging;Neuronal Plasticity;neuroregulation;Neurosciences;novel;novel strategies;Outcome;Participant;Patient Self-Report;Patients;placebo group;Population;Prefrontal Cortex;Prevalence;Process;Psychotherapy;Randomized;randomized, clinical trials;recruit;Reporting;Research;Research Personnel;Research Project Grants;Research Training;response;Role;Running;Self Assessment;Severities;Signal Transduction;skill acquisition;skills;social;success;System;Techniques;Testing;Therapeutic;Therapeutic Uses;Thermometers;Time;Training;translational scientist;treatment response;Visual;Vocation;Work;young adult

PROJECT_TITLE: Neurofeedback-enhanced cognitive reappraisal training for young adults with anxiety

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Neurosciences;Women's Health Research

ORG_CITY: TYLER

ORG_NAME: UNIVERSITY OF TEXAS TYLER

ORG_STATE: TX

PHR: PROJECT NARRATIVE  Human Epidermal growth factor Receptor-2 (HER2) is a clinically validated target that is upregulated in 25% of invasive breast cancers and associated with poor disease prognosis. This project will characterize small molecules predicted by computer modeling to inhibit HER2 with a novel mechanism and verified to be selective and effective in inhibiting HER2+ cell lines. The expected findings will meet NIH's mission to reduce illness by validating this class of molecules for breast cancer treatment.

PI_NAMEs: ABDELAZIZ, MAY H. (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Affinity;Alternative Splicing;analog;Animal Model;Antibodies;Antineoplastic Agents;Binding;Binding Sites;Biochemical;Biological Assay;Biological Availability;Biophysics;blood-brain barrier crossing;blood-brain barrier penetration;Brain;Breast Cancer Treatment;cancer cell;Cancer cell line;Cancer Etiology;cancer therapy;Cardiotoxicity;Catalytic Domain;Cell Line;Cells;Cellular Assay;Cessation of life;Clinical;Colorectal Cancer;Combined Modality Therapy;Computer Models;Cytoplasmic Protein;dimer;Dimerization;disease prognosis;Doctor of Pharmacy;drug discovery;Drug Targeting;Drug usage;Effectiveness;Eligibility Determination;Environment;Epidermal Growth Factor Receptor;ERBB3 gene;ErbB4 gene;experience;Extracellular Domain;Family;Feedback;Funding;Future;Genes;Goals;Growth;Homo;Human;immunogenicity;in silico;In Vitro;in vivo;in vivo Model;inhibitor;innovation;Institution;Investigational New Drug Application;Label;lapatinib;Lead;Legal patent;Life;Ligand Binding;Malignant Breast Neoplasm;Malignant neoplasm of brain;Malignant neoplasm of lung;Malignant Neoplasms;malignant stomach neoplasm;Mediator;member;Metastatic malignant neoplasm to brain;Mission;Mitogens;Modeling;molecular modeling;Mutate;Mutation;Neoplasm Metastasis;novel;novel strategies;Oncogenic;Outcome Study;overexpression;patient population;Patients;Pharmaceutical Preparations;Pharmacotherapy;phase I trial;Phosphorylation;Phosphotransferases;Plasma;Point Mutation;prediction algorithm;predictive modeling;prevent;Property;receptor;Receptor Activation;Receptor Inhibition;Relapse;Research;research clinical testing;Research Support;Resistance;Signal Transduction;Site;small molecule;Solid Neoplasm;success;Surface;targeted agent;targeted treatment;Techniques;Testing;Texas;Therapeutic;Therapeutic antibodies;therapy resistant;Toxic effect;Training;translational potential;Trastuzumab;Treatment Failure;tumor;tumor progression;undergraduate student;United States National Institutes of Health;Universities;Validation;virtual screening;Woman;Work

PROJECT_TITLE: Characterization of HER2 inhibitors with a novel mechanism of action

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDPT-J (80)]


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

ORG_CITY: INDIANAPOLIS

ORG_DEPT: GENETICS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Alzheimer’s disease (AD) is a highly prevalent disorder for which there are no effective therapies. This application identifies a new genetic locus that confers increased risk for AD and is linked to the innate immune response observed in the disease. This application proposes to develop and characterize new mouse models of AD possessing genetic variants of the gene PLCG2 and determine how the variants affects disease pathogenesis to inform the therapeutic targeting of this enzyme.

PI_NAMEs: BISSEL, STEPHANIE J;LAMB, BRUCE T (contact);LANDRETH, GARY E.

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: Acceleration;Affect;Alleles;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease risk;Attenuated;Behavioral;Biological Assay;Biology;Brain;brain tissue;cell type;Cells;Central Nervous System Diseases;Cessation of life;Chronic Lymphocytic Leukemia;Cognition;Complex;cytokine;Data;Development;Disease;Disease Progression;Drug resistance;effective therapy;Elements;Enzymes;Exhibits;experimental study;gain of function;Gene Expression;Gene Expression Profile;Genes;Genetic study;Genetic Transcription;genetic variant;genome wide association study;genomic locus;Human;human induced pluripotent stem cells;immune function;Immune response;Immune signaling;Immunologic Receptors;Impaired cognition;Impairment;improved;Individual;Innate Immune Response;Investigation;Knock-out;Laboratories;Link;loss of function;Macrophage;Maps;Measures;Mediating;Membrane;Memory;Microglia;mild cognitive impairment;Modeling;Molecular;Molecular Profiling;mouse model;Mus;Neurodegenerative Disorders;Neurons;novel;Pathogenesis;Pathology;Pathway Analysis;Pathway interactions;Patients;Performance;Phagocytes;Phenotype;PLCG2 gene;Risk;risk variant;Rodent Model;Role;Severity of illness;Signal Pathway;Signal Transduction;tau Proteins;tau-1;Testing;Therapeutic;therapeutic target;Time;Tissue-Specific Gene Expression;transcription factor;Transcriptional Regulation;TREM2 gene;Variant;β-amyloid burden

PROJECT_TITLE: Impact of PLCG2 Alzheimer's Disease Risk Variants on Microglia Biology and Disease Pathogenesis

STUDY_SECTION: CDIN

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


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: LEXINGTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: Tauopathies consist of a group of neurodegenerative diseases, including Alzheimer’s disease (AD) and currently no therapeutic treatments exist for tauopathies. Post-translational modifications (PTMs) of tau are thought to play important mechanistic roles and could serve as a target strategy. This study will test how the citrullination pathway of tau impacts tau biology and neuropathology in vitro and in vivo, which may provide a new foundation for citrullination during tauopathies and AD.

PI_NAMEs: LEE, DANIEL CARL (contact)

PROGRAM_OFFICER_NAME: YANG, AUSTIN JYAN-YU

PROJECT_TERMS: Affect;Age;age related;aging related;Alzheimer's Disease;Amino Acid Substitution;Animal Model;Animals;Area;Arginine;Arginine deiminase;Behavior;Behavioral;Binding;Biochemical;Biochemistry;Biology;Biosensor;Cell model;cell type;Cells;Charge;Client;Clinical;Cognition;conditional knockout;conformer;dimer;Disease;Electrophysiology (science);Epitopes;extracellular;Fostering;Foundations;gain of function;Genes;Goals;Human;Impaired cognition;improved;In Vitro;in vivo;in vivo evaluation;Knock-out;Knockout Mice;Knowledge;Long-Term Potentiation;loss of function;Metabolism;Microdialysis;Microtubule Polymerization;Microtubules;Modeling;Molecular Conformation;Molecular Target;monomer;Mus;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;neurofibrillary tangle formation;Neurofibrillary Tangles;Neurons;neuropathology;novel;overexpression;Pathogenesis;Pathologic;Pathology;Pathway interactions;Phenotype;Phosphorylation;Play;polymerization;Polymers;Post-Translational Protein Processing;prevent;protein structure;Proteins;Research;Risk;Role;Site;spatiotemporal;Structure;Syndrome;tau aggregation;tau function;tau interaction;tau Proteins;tau-1;Tauopathies;Techniques;Testing;Therapeutic;Tissues;Tubulin;Work

PROJECT_TITLE: Emerging Role of Tau Citrullination During Alzheimer’s disease and Tauopathies


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;Human Genome;Neurodegenerative;Neurosciences;Prevention

PHR: PROJECT NARRATIVE Alzheimer's Disorder (AD) is one of the most pressing public health issues as the world's population continues to age, but there is no known effective prevention or cure exists. The Alzheimer's Disease Sequencing Project (ADSP) has sequenced a large number (n>17,000) of AD patients and normal healthy elderly controls. Leveraging the rich resources from ADSP, we propose to comprehensively detect genomic copy number variations (CNVs), find CNV and AD association for different ethnicities, and further facilitate the identification of genetic therapeutic strategies.

PI_NAMEs: LEE, WAN-PING  (contact);TZENG, JUNG-YING

PROGRAM_OFFICER_NAME: BENNANI-BAITI, MICHAEL

PROJECT_TERMS: Address;Affect;Age;Algorithms;Alzheimer's Disease;Alzheimer's disease risk;American;Amyloid Beta A4 Precursor Protein;Architecture;Bioconductor;case control;Categories;Chromosomes;Code;Cognitive;cohort;Collaborations;computational pipelines;Copy Number Polymorphism;Data;Data Collection;Databases;Dementia;Disease;disorder risk;dosage;Down's Syndrome;effective intervention;Elderly;Environmental Risk Factor;Ethnic Origin;Ethnic Population;Etiology;Frequencies;functional genomics;Gene Dosage;Gene Frequency;Genes;Genetic;Genetic Diseases;Genetic study;Genome;genome sequencing;genome wide association study;genome-wide;genomic locus;Genomic Segment;Genomics;Genotype;Goals;Hereditary Disease;Heritability;Heterogeneity;Image;Individual;innovation;insertion/deletion mutation;insight;Investigation;Joints;Knowledge;Length;Life Style;Literature;Meta-Analysis;Methods;Molecular;multi-ethnic;Neurodegenerative Disorders;neuropathology;new therapeutic target;Not Hispanic or Latino;Nucleotides;open source;Outcome;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Population;Positioning Attribute;Prevention;Public Health;reduce symptoms;Resolution;Resources;Risk;risk prediction;risk variant;Role;Sampling;Scientist;Single Nucleotide Polymorphism;Source Code;Standardization;Technology;Testing;Therapeutic;therapeutic target;trial design;Validation;Variant;variant detection;whole genome

PROJECT_TITLE: Copy Number Variation Identification and Association Study on Alzheimer's Disease Whole Genome Sequencing Data

STUDY_SECTION: NAME

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


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);Brain Disorders;Cerebrovascular;Climate-Related Exposures and Conditions;Dementia;Genetics;Lung;Neurodegenerative;Neurosciences;Pulmonary Fibrosis

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: Project Narrative Traffic-related air pollution has been associated with an increased risk for Alzheimer’s disease (AD); however, the vehicular emissions components responsible for this effect, and the mechanism(s) by which air pollution promotes AD remain largely unknown. To answer these questions, we will expose rats expressing human AD susceptibility genes in real-time to air pollution from a major freeway and compare the effects of gases vs. particulate matter from light vs. heavy duty vehicles on their lungs and brains, and determine whether lung inflammation leads to changes in the brain. These studies are needed to corroborate human studies linking traffic- related air pollution exposure to increased risk for AD, and to inform regulatory and health interventions to reduce AD risk for individuals living, working, or attending school near busy roadways.

PI_NAMEs: BEIN, KEITH ;LEIN, PAMELA J (contact);VAN WINKLE, LAURA S

PROJECT_TERMS: Acceleration;Address;Adverse effects;Age;age effect;Age Months;Age of Onset;age related neurodegeneration;air filter;Air Pollution;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease risk;ambient particle;Amyloid beta-Protein;Animal Feed;Animal Model;Animals;Behavior;Blood;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Brain;brain endothelial cell;Bronchoalveolar Lavage Fluid;Calcium Signaling;Cells;Characteristics;Chronic;Clinical;Clinical Trials;Cognitive;Cognitive deficits;Collagen;congenic;Consensus;Data;Dementia;dementia risk;density;Deposition;design;Diesel Exhaust;Disease;disease phenotype;Endothelium;epidemiology study;exhaust;Exposure to;FDA approved;Female;Fibroblasts;Future;Gases;gene environment interaction;genetic risk factor;glial activation;Grant;Health;Human;human model;Immune;Impaired cognition;Individual;Inflammation;Inflammation Mediators;inhibitor;Intervention;Ion Channel;Late Onset Alzheimer Disease;Light;Link;Lung;male;Measures;Mediating;Mesenchymal;Microglia;Modeling;motor behavior;Mus;Nerve Degeneration;Neurofibrillary Tangles;neuroinflammation;neuron loss;Oral;Outcome;overexpression;particle;Particulate;Particulate Matter;Pathogenesis;Pathology;Pharmaceutical Preparations;Phenotype;Pirfenidone;pollutant;pre-clinical;preclinical study;Predisposition;preservation;Production;Publishing;Pulmonary Fibrosis;Pulmonary Inflammation;Pulmonary Pathology;pyridine;Rat Transgene;Rattus;Regulation;Reporting;Rodent;Role;Schools;Secondary to;Senile Plaques;Severities;sex;Sheep;side effect;Signal Transduction;spatiotemporal;Susceptibility Gene;Synapses;System;Tauopathies;Testing;Time;traffic-related air pollution;Transforming Growth Factor beta;United States;uptake;Vehicle Emissions

PROJECT_TITLE: Traffic-related air pollution exacerbates AD-relevant phenotypes in a genetically susceptible rat model via neuroinflammatory mechanism(s)

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


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;Social Determinants of Health

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: Project Narrative A central question in aging and Alzheimer's disease (AD) is when (and if so, how) neural substrates underlying decision-making are altered and whether impairment in decision-making can be attenuated or halted. This effort seeks to uncover the role of aging, sex and AD-associated pathology on economic decision-making in mice. To uncover whether and how Aβ-dependent mechanisms induce changes in circuits underlying various forms of decision-making, we will use mouse models of AD combined with a unique behavioral platform designed to resolve decision-making complexities, whole-brain imaging and three parallel interventions (genetic, pharmacologic and optogenetic).

PI_NAMEs: THOMAS, MARK JOHN (contact)

PROJECT_TERMS: Ablation;Adult;Age;age effect;Age Months;age related decline;Age Years;Aging;aging population;aging related disease;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease risk;American;Amyloid;Amyloid beta-Protein;Area;Attention;Attenuated;Behavior;Behavioral;behavioral economics;Behavioral Paradigm;Brain;Brain imaging;Brain region;Cognitive;cognitive function;Corpus striatum structure;Data;Decision Making;Dementia;design;Economics;Elderly;empowerment;Environment;extracellular;Female;Functional disorder;Funding;Genes;Genetic;Health;Healthcare;Hippocampus;human old age (65+);hyperphosphorylated tau;Impairment;improved;Individual;interdisciplinary approach;Intervention;J20 mouse;Joints;Judgment;Knock-in Mouse;Lesion;Levetiracetam;Life;Life Expectancy;male;Medial;Medical;Medicine;memory process;memory recall;middle age;Modeling;Motivation;mouse model;mRNA Expression;Mus;neural;Neurofibrillary Tangles;neuroimaging;Neurons;neuropathology;Neurosciences;non-genetic;normal aging;novel;older adult;Older Population;optogenetics;pathological aging;Pathology;pharmacologic;Pharmacologic Substance;pre-clinical;prodromal Alzheimer's disease;protein expression;Proteins;Psychology;Qualifying;Reporting;Retirement;Rewards;Role;Senile Plaques;sex;social;socioeconomics;Structure;Synapses;tau aggregation;tau Proteins;Testing;Time;Toxin;Transgenic Mice;Wild Type Mouse;young adult

PROJECT_TITLE: Decision-making alterations in mouse models of Alzheimer's disease


ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative As the burden of Alzheimer’s disease in the United States and worldwide is high, there is a critical need to develop novel PET ligands to image illness-related biological processes in the brain. This work will develop key imaging tools designed to advance the scientific understanding of GluA2-specific AMPA receptor in the ionotropic glutamate system and facilitate the discovery of neurotherapeutics for Alzheimer’s disease patients.

PI_NAMEs: LIANG, STEVEN H (contact)

PROGRAM_OFFICER_NAME: GROTHAUS, PAUL G

PROJECT_TERMS: ABCB1 gene;Affinity;Alzheimer's Disease;Alzheimer's disease patient;AMPA Receptors;Autopsy;Autoradiography;Binding;Biochemical Process;Biodistribution;Biological;Biological Assay;Biological Process;Blood specimen;Brain;brain tissue;Central Nervous System;Characteristics;Chemistry;Clinical;clinical translation;design;Development;Docking;Dose;drug discovery;Evaluation;Excitatory Synapse;Functional disorder;Generations;glutamatergic signaling;Glutamates;Goals;Human;Image;image translation;Imaging Device;imaging study;improved;In Vitro;in vitro Assay;in vivo;in vivo evaluation;Kinetics;Knockout Mice;Label;Lead;Learning;Libraries;Ligands;Long-Term Potentiation;Mediating;Memory;Messenger RNA;Metabolic Clearance Rate;Modeling;Molecular;Monitor;mouse model;National Institute of Mental Health;Neurodegenerative Disorders;neurotransmission;nonhuman primate;novel;Parents;Permeability;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Positioning Attribute;Positron;Radioactivity;Radiolabeled;radioligand;receptor;receptor expression;response;Rodent;Scientific Advances and Accomplishments;Site;Specificity;stable cell line;System;Testing;Therapeutic;Transducers;Transgenic Organisms;Translations;United States;uptake;Validation;Western Blotting;Work

PROJECT_TITLE: AMPAR ligand discovery for Alzheimer's disease

STUDY_SECTION: DDNS

STUDY_SECTION_NAME: Drug Discovery for the Nervous System Study Section[DDNS-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);Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative  Recent evidence suggests that breakdown of the blood-brain barrier (BBB) is an important process in the pathogeneisis of Alzheimer's disease and related dementia (ADRD). However, the relationship between BBB damage and other pathogenic events in ADRD are not clear. This project will use cutting-edge BBB imaging techniques, assays, and animal models to systematically investigate BBB dysfunction in humans and animal models in both cross-sectional and longitudinal settings.

PI_NAMEs: LU, HANZHANG  (contact)

PROGRAM_OFFICER_NAME: NEWMAN, ELIZABETH

PROJECT_TERMS: Affect;Albumins;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease related dementia;Amyloid;Amyloid beta-42;Amyloid beta-Protein;Animal Model;Arterial Disorder;Autopsy;autosome;Biological Assay;Blood;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood Vessels;blood-brain barrier function;blood-brain barrier permeabilization;Brain;brain tissue;Cells;Cerebral small vessel disease;Cerebrospinal Fluid;cerebrovascular reactivity;Cerebrum;clinically relevant;Cognition;Cognitive;cognitive function;Contrast Media;cytokine;Dementia;Dextrans;disease model;Elderly;Enrollment;Event;Experimental Models;follow-up;Gadolinium;Goals;Human;human model;human study;imaging biomarker;imaging study;Imaging Techniques;Impaired cognition;in vivo;Individual;Inflammation;inflammatory marker;Interleukin-6;Laboratories;Literature;longitudinal design;Magnetic Resonance Imaging;Measures;Memory;Microvascular Dysfunction;mild cognitive impairment;Modeling;Molecular Weight;mouse model;multidisciplinary;multimodality;Mus;Neuropsychological Tests;non-invasive imaging;novel;Participant;Pathogenesis;Pathogenicity;Pathologic;Pathologic Processes;Pathology;Patients;Permeability;Plasma;Process;Proteins;Rodent Model;Role;Serum Albumin;Smooth Muscle Myocytes;Subcortical Infarctions;Subcortical Leukoencephalopathy;tau aggregation;tau Proteins;tau-1;Techniques;Time;TNF gene;Transgenic Mice;Transgenic Organisms;Validation;Vascular Endothelium;vascular injury;vascular risk factor;Water;β-amyloid burden

PROJECT_TITLE: Blood-brain barrier dysfunction in Alzheimer's disease: from humans to animal models

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


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;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Although great progress in recent years has been made in defining key innate immune receptors involved in Alzheimer’s disease, our knowledge of the specific intracellular signaling molecules that coordinate immune responses in Alzheimer’s disease remains poorly defined. In our preliminary studies, we have identified previously undescribed roles for the innate immune signaling adaptor CARD9 in an amyloid beta-mediated mouse model of Alzheimer’s disease. For this project, we will further define roles for CARD9 and the CARD9- associated kinase SYK in the innate immune response to amyloid beta and we will also evaluate the therapeutic efficacy of using SYK/CARD9-activating agents to limit Alzheimer’s-related disease progression.

PI_NAMEs: LUKENS, JOHN R (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: abeta accumulation;Abeta clearance;abeta deposition;Ablation;Acceleration;Affect;age related;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Amyloid beta-Protein;Animal Disease Models;autoinflammatory diseases;Brain;CD22 gene;Cell Death;Cell Line;Cells;Cognition;Cognitive deficits;cytokine;Dementia;Disease;disease model;Disease Progression;Experimental Models;Genetic;genome wide association study;Human;Human Genome;human induced pluripotent stem cells;Immune response;Immune signaling;Immunologic Receptors;Impaired cognition;Impairment;In Vitro;in vivo;Individual;induced pluripotent stem cell;Infection;inhibitor;Innate Immune Response;Innate Immune System;insight;interest;Knowledge;loss of function;loss of function mutation;Macrophage;Mediating;Mediator;Microglia;Modeling;Molecular;mouse model;Mouse Strains;Mus;Mutation;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;neuroinflammation;neuropathology;neuroprotection;neurotoxic;new therapeutic target;novel;Pathogenesis;Pathology;Pathway interactions;patient derived induced pluripotent stem cells;Patients;Phagocytosis;pharmacologic;Phosphotransferases;Production;protective effect;receptor;response;Role;Senile Plaques;Signal Pathway;Signal Transduction;Signaling Molecule;SYK gene;System;Testing;Therapeutic;transcriptomics;Transgenic Mice;Treatment Efficacy;TREM2 gene;Work

PROJECT_TITLE: Role of the SYK-CARD9 signaling axis in Alzheimer's disease

STUDY_SECTION: CMBG

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


PHR: Project Narrative Many lipid mediators generated from the metabolism of long-chain polyunsaturated fatty acids have potent activities in regulating inflammation. We intend to test an approach to preserve the anti-inflammatory actions of epoxy fatty acids by inhibiting their degrading enzyme, soluble epoxide hydrolase (sEH). We hypothesize a sEH-regulated brain-liver axis model and will determine if sEH dysfunction in microglia and liver contributes to Alzheimer’s disease.

PI_NAMEs: JIN, LEE-WAY ;MAEZAWA, IZUMI  (contact)

PROJECT_TERMS: abeta oligomer;Acids;Affect;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Animal Model;Anti-Inflammatory Agents;Apolipoprotein E;apolipoprotein E-3;apolipoprotein E-4;APP-PS1;autocrine;Brain;Cells;Cerebrospinal Fluid;Chemical Actions;chemical stability;Code;Cytochrome P450;Data;data modeling;Development;Disease Progression;Enzymes;Epoxide hydrolase;Fatty Acids;Functional disorder;Genes;Genotype;Glycols;Hepatic;Hepatocyte;High Density Lipoproteins;Human;human induced pluripotent stem cells;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Knock-out;knockout gene;Link;lipid mediator;lipid metabolism;lipidomics;Lipids;Lipopolysaccharides;Lipoproteins;Liver;Low-Density Lipoproteins;Mediating;Metabolism;metabolomics;Microglia;Modeling;Molecular;Mus;Neuroglia;neuroinflammation;neuroprotection;Neurotoxins;non-demented;paracrine;Pathway interactions;Pattern;Phenotype;Plasma;Polyunsaturated Fatty Acids;preservation;Property;Proteins;PTGS2 gene;Rattus;Regulation;response;Rodent;Rodent Model;Sampling;Signal Pathway;Signal Transduction;Signaling Molecule;Specimen;Structure;Supplementation;Surveys;Testing;Therapeutic;transcriptomics;Very low density lipoprotein;Work

PROJECT_TITLE: Soluble epoxide hydrolase-regulated lipid signaling in Alzheimer’s disease

STUDY_SECTION: NOMD

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


ORG_CITY: NEW YORK

ORG_DEPT: NEUROLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: PROJECT NARRATIVE This proposal is clinically important by focusing on memory circuits that are differentially affected in Alzheimer disease. By interrogating their changes at multiple levels, from molecular to in vivo function, the results of this work will provide a more sophisticated understanding of disease pathophysiology and breakdown of information flow in this region. This will enable novel strategies to improve memory in human patients.

PI_NAMEs: MASURKAR, ARJUN VIJAY (contact)

PROGRAM_OFFICER_NAME: GRAY, ERIN EMILY

PROJECT_TERMS: 3xTg-AD mouse;Address;Affect;aged;Aging;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's Disease Pathway;Alzheimer's disease patient;Amyloid;Area;Behavior;Biological;Calcium;calcium indicator;cell type;Cells;Clinical;Code;Cognition;Data;Development;Disease;Disease Marker;Disease Pathway;Dorsal;Electrophysiology (science);entorhinal cortex;Epilepsy;Equilibrium;Exhibits;Functional disorder;Gene Expression;hippocampal pyramidal neuron;Hippocampus;Human;Image;improved;In Vitro;in vivo;in vivo evaluation;innovation;Ischemia;Knowledge;Lateral;Link;Literature;Maps;Measures;Medial;Memory;Memory impairment;Memory Loss;Methods;Modeling;Molecular;molecular marker;Mus;Nature;Nerve Degeneration;network dysfunction;Neurofibrillary Tangles;neuronal circuitry;Neurons;novel strategies;operation;Output;Pathologic;pathological aging;Pathology;Patients;Physiological;Population;Positioning Attribute;Predisposition;Process;Property;Proteins;Proteome;Proteomics;Publishing;reduce symptoms;Research Personnel;Risk Factors;Role;Severity of illness;Shapes;Slice;Symptoms;Synapses;tau Proteins;Testing;Work

PROJECT_TITLE: Differential impact of Alzheimer disease on neuronal subpopulations in dorsal hippocampal CA1


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

ORG_CITY: HERSHEY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: Project Narrative Mitochondrial permeability transition is a key event in the induction of cell death during the progression of neurodegenerative disease. This project will determine the single-particle cryo-EM structure of ATP synthase c-subunit leak channel that houses the pore of the mitochondrial permeability transition. The successful completion of the proposed project will result in novel therapies and preventative strategies for Alzheimer's disease by targeting the ATP synthase leak channel.

PI_NAMEs: MNATSAKANYAN, NELLI  (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: abeta accumulation;Affinity;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Amyloid beta-Protein;Architecture;BCL2L1 gene;Binding;Biology;Brain;Calcium;Cell Death;Cell Death Induction;Cell Survival;Complex;Cryo-electron tomography;Cryoelectron Microscopy;cyclophilin D;cytochrome c;Detergents;Development;driving force;Energy Metabolism;Environment;Event;Functional disorder;Glutamates;Goals;Hippocampus;Human;Immobilization;In Situ;Individual;inhibitor;Inner mitochondrial membrane;Interferometry;Kinetics;Lipids;Liposomes;Literature;Measures;Membrane;Mitochondria;mitochondrial dysfunction;mitochondrial membrane;mitochondrial permeability transition pore;Mitochondrial Proton-Translocating ATPases;Modeling;Molecular;Molecular Conformation;monomer;mouse model;Mus;N-terminal;nanodisk;Nerve Degeneration;Neurodegenerative Disorders;Neurons;novel;novel therapeutics;Oligomycins;Outer Mitochondrial Membrane;overexpression;particle;patch clamp;Pathogenesis;Pathologic;Pathway interactions;Permeability;pharmacologic;Play;prevent;Prevention strategy;Property;Proteins;reconstitution;Reporting;Research;Resolution;Role;Rupture;sensor;Signal Transduction;Structure;Synapses;System;Testing;time use;Toxic effect;Transgenic Mice

PROJECT_TITLE: Structural and functional characterization of ATP synthase c-subunit leak channel and its role in AD pathogenesis

STUDY_SECTION: BPNS

STUDY_SECTION_NAME: Biophysics of Neural Systems Study Section[BPNS-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;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Lymphatic Research;Neurodegenerative;Neurosciences;Physical Activity;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Public Health Relevance: Numerous studies support the association between glymphatic clearance and Alzheimer’s disease (AD), which is a slowly progressive, irreversible neurodegenerative disease with a long preclinical phase; aging is the major prevalence factor of AD. The project aims to develop an advanced non- invasive, non-contrast MRI biomarker to identify egress pathways and quantitative intrinsic cerebrospinal fluid (CSF) outflow metrics in mild cognitive impairment (MCI) and AD patients, compared with age-, sex-matched healthy subjects. We will also investigate changes in egress pathways of intrinsic CSF outflow in healthy, MCI, and AD subjects with different physical activity levels using actigraphy.

PI_NAMEs: MIYAZAKI, MITSUE  (contact)

PROJECT_TERMS: 3-Dimensional;abeta accumulation;Abeta clearance;abeta deposition;Acceleration;actigraphy;Address;Adult;Affect;Age;age related decline;Aging;Alzheimer's Disease;Alzheimer's disease patient;American;Amyloid beta-Protein;Animals;Blood - brain barrier anatomy;Blood Vessels;Brain;brain tissue;Cardiac;Central Nervous System;Cerebral hemisphere;Cerebrospinal Fluid;cerebrospinal fluid clearance;cerebrospinal fluid flow;Circulation;Cognitive;cognitive function;cohort;Contrast Media;Dementia;Disease;Drainage procedure;Dura Mater;Early Diagnosis;Early Intervention;Evaluation;experience;Extracellular Space;Female;Functional disorder;Gadolinium;glymphatic clearance;glymphatic dysfunction;glymphatic system;Goals;Human;human old age (65+);hyperphosphorylated tau;Impaired cognition;improved;in vivo;Individual;Injections;Intercellular Fluid;interest;Intrathecal Injections;Left;Left cerebral hemisphere;Liquid substance;Long-Term Care;lymphatic vessel;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;male;Measurement;Measures;Meninges;Metabolic Pathway;Methodology;Methods;mild cognitive impairment;Monitor;Morbidity - disease rate;mortality;Neurodegenerative Disorders;Neurofibrillary Tangles;Neurons;neuropathology;nonhuman primate;novel;old mice;older adult;Pathologic;Pathway interactions;Patient Monitoring;Patients;Persons;Phagocytosis;Phase;Physical activity;Physiologic pulse;Positron-Emission Tomography;pre-clinical;preference;Prevalence;Progressive Disease;Proteins;public health relevance;Rattus;Reporting;Respiration;Rodent;Rodent Model;Role;Sagittal Sinus;sedentary;Senile Plaques;sex;Sex Behavior;Side;Signal Transduction;Site;Sleep;Spin Labels;Superior sagittal sinus;Symptoms;System;Techniques;Testing;Time;Tracer;Translations;uptake;Visualization;Waste Products;wasting;women subjects

PROJECT_TITLE: Intrinsic CSF outflow metrics for mild cognitive impairment and Alzheimer's disease


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

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE  Microbial infection has been recently proposed as a risk factor for Alzheimer’s disease (AD). In this project we will evaluate whether peripheral infection mediated by sepsis and brain infection induced by meningitis represent a causal component of AD. This hypothesis will be explored using established models of infection and AD, and a battery of established and novel biochemical, immunohistochemical and imaging assays.

PI_NAMEs: BARICHELLO, TATIANA ;MORALES, RODRIGO  (contact)

PROJECT_TERMS: abeta accumulation;abeta deposition;Acceleration;Acute;adaptive immune response;Affect;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease risk;American;Amyloid;Amyloid beta-42;Amyloid beta-Protein;Amyloid deposition;Animal Model;Animals;APP-PS1;Astrocytes;Bacteria;Bacterial Meningitis;Behavioral;Biochemical;Biological;Biological Assay;Blood;blood-brain barrier permeabilization;Body Fluids;Bone Marrow Transplantation;Brain;cecal ligation puncture;Cells;Central Nervous System;Cerebrospinal Fluid;Cerebrum;Chronic;cisterna magna;Clinical;Cognition;cognitive performance;Communicable Diseases;Data;Dementia;Deposition;Development;Diagnosis;Disease;Disease Progression;Encephalitis;epidemiologic data;Euthanasia;Event;experimental study;glial activation;Goals;high risk;Human;hyperphosphorylated tau;Image;Immune;Immune system;Impaired cognition;in vivo;Individual;Infection;Infectious Agent;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;Injections;insight;Late Effects;Link;Liquid substance;Long-Term Effects;Measures;Mediating;Meningitis;microbial;misfolded protein;Modality;Modeling;Molecular;mouse model;Mus;Nerve Degeneration;neurofilament;neurofilament protein L;Neurologic;nonalzheimer dementia;novel;novel strategies;Onset of illness;Operative Surgical Procedures;Outcome;overexpression;pathogen;Pathogenesis;Pathologic;Pathology;Patients;Peripheral;Play;Positron-Emission Tomography;prevent;Process;Production;protein misfolding cyclic amplification;Proteins;receptor expression;receptor for advanced glycation endproducts;Recovery;Reporter;Research;Risk;Risk Factors;Rodent;Role;Sampling;Secondary to;Sepsis;septic;septic patients;Series;Serotyping;Streptococcus pneumoniae;Survival Rate;Survivors;Suspensions;systemic inflammatory response;tau aggregation;tau Proteins;tau-1;Technology;Testing;Time;Transgenic Mice;Viral

PROJECT_TITLE: Infection-driven mechanisms associated with Alzheimer's disease pathology


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Dementia;Epilepsy;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Prevention

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it develops a new biomarker to predict early stages of Alzheimer’s disease (AD) using machine learning technology applied to cutting-edge dry-electrode ambulatory electroencephalography data. Prediction will rely on the development and validation of a state-of- the-art system that combines epileptogenic activity and functional brain networks. Once such a biomarker has been developed, this will provide the basis for a noninvasive, inexpensive, and portable AD screening tool that can be easily deployed in-home or in residential communities.

PI_NAMEs: FUNKE, MICHAEL ;MOSHER, JOHN COMPTON (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: Acceleration;Address;Alzheimer disease detection;Alzheimer disease screening;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer’s disease biomarker;amnestic mild cognitive impairment;Amyloid;Behavioral;Biological;Biological Markers;biomarker evaluation;Brain;Clinical;clinical predictors;cohort;Collaborations;combinatorial;Communities;cost;Data;Data Analyses;deep learning;deep learning model;Dementia;design;Development;digital;Digital biomarker;digital solutions;Disease;Disease Progression;Dryness;early detection biomarkers;Early Diagnosis;Electrodes;Electroencephalography;Electrophysiology (science);Engineering;Epilepsy;epileptiform;Equilibrium;Event;follow-up;Frequencies;General Population;Goals;Graph;Health Sciences;Home;Impaired cognition;Individual;innovation;Institution;Joints;Lead;Learning;Link;Location;Machine Learning;Magnetic Resonance Imaging;Magnetoencephalography;Measures;Methods;Modeling;Molecular;Monitor;Morphology;multimodal learning;multimodality;Neurobehavioral Manifestations;neurophysiology;novel;Outcome;Patient Monitoring;Patient-Focused Outcomes;Patients;personalized predictions;Persons;portability;Positron-Emission Tomography;predictive marker;Preparation;Prevalence;prodromal Alzheimer's disease;prognostication;prospective;Protocols documentation;Public Health;real world application;Research;Research Project Grants;Residential Facilities;Risk;Role;Screening procedure;Seizures;Signal Transduction;Standardization;Symptoms;System;Technology;Testing;Texas;tool;Toxic effect;trait;Universities;Validation

PROJECT_TITLE: Digital biomarker for a low cost ambulatory test for early detection of Alzheimer's disease


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

ORG_CITY: BLACKSBURG

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

PHR: Project Narrative Alzheimer's disease progression has been linked to changes in overall bulk fluid flow into and out of the brain. At the cellular level, the fluid flow that cells feel is called interstitial fluid flow, and it's role in Alzheimer's is, as yet, unstudied. Here we will measure, manipulate, and model interstitial fluid flow as it relates to increases in Alzheimer's pathology and alleviation of associated symptoms.

PI_NAMEs: MUNSON, JENNIFER M (contact)

PROJECT_TERMS: 3-Dimensional;abeta accumulation;abeta deposition;Abeta synthesis;Address;Affect;Aging;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid;Amyloid beta-Protein;Amyloidosis;Animals;apolipoprotein E-4;associated symptom;Astrocytes;behavior test;Binding;Biological Models;Biomedical Engineering;Blood;Brain;Brain imaging;Brain Injuries;brain tissue;cancer cell;cell motility;Cell surface;Cells;Cellular biology;Cerebrospinal Fluid;Cerebrovascular system;Cognitive deficits;Computational algorithm;computer framework;Computer Models;Coupled;design;Development;Diagnosis;Disease;disease model;disease phenotype;Disease Progression;Drainage procedure;Etiology;fluid flow;genetic risk factor;glymphatic system;Grant;Harvest;Health;healthy aging;high risk;Hippocampus;Human;human model;Hydrogels;imaging approach;imaging modality;Impaired cognition;Impairment;In Vitro;in vitro Model;in vivo;in vivo imaging system;Individual;Inflammatory;insight;Intercellular Fluid;interstitial;intravital imaging;Invaded;J20 mouse;Knock-out;Late Onset Alzheimer Disease;Lead;Link;Lipids;Liquid substance;Longitudinal Studies;Lymphatic function;Malignant neoplasm of brain;Malignant Neoplasms;Measurement;Measures;Mediating;Mediator;Memory Loss;Meningeal lymphatic system;Methods;Microfluidics;Microglia;Microscopy;Modality;Modeling;Molecular Biology;mouse model;Mus;Nerve Degeneration;neural;neurofibrillary tangle formation;Neuroglia;Neurons;neuroprotection;neurotransmission;Normal Cell;novel;Pathogenesis;Pathologic;Pathway interactions;patient derived induced pluripotent stem cells;Pattern;Peptides;pharmacologic;Physics;Physiological;pressure;Production;receptor;Reporting;response;Risk Factors;Role;Route;Senile Plaques;Series;shear stress;Signal Induction;Signal Transduction;Slice;sphingosine 1-phosphate;Sphingosine-1-Phosphate Receptor;System;tau aggregation;Therapeutic;Tissue Engineering;Tissue imaging;Tissues;trafficking;Transgenic Mice;tumor;tumor microenvironment;VEGFC gene;Work

PROJECT_TITLE: Interstitial fluid flow in Alzheimer's Disease Progression


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;Human Genome;Neurodegenerative;Neurosciences

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE Studies proposed here aim to investigate the mechanisms of how immunoproteasome deficiency in activated glial cells exacerbates amyloid and tau pathology and spread in Alzheimer’s disease in vivo and in vitro. Employing single-nucleus RNA-sequencing (snRNAseq) and quantitative proteomics, we aim to elucidate the role of immunoproteasome deficiency in differential gene expression, proteome, and pathways in AD models and the aging brain.

PI_NAMEs: MYEKU, NATURA  (contact)

PROJECT_TERMS: Address;Affect;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Amyloid;amyloid pathology;Biogenesis;cell type;Cells;Coculture Techniques;Cognition;Complex;cytokine;Data Set;Deterioration;Disease;Disease Progression;Etiology;Exhibits;extracellular;Feedback;Gene Expression;Genes;Goals;Hydrophobicity;Immune;immune function;Immune response;Impairment;In Vitro;in vivo;Inflammatory;Inflammatory Response Pathway;Interferon Type II;Knock-in Mouse;Mass Spectrum Analysis;Mediating;MHC Class I Genes;Microfluidic Microchips;Modeling;mouse model;multicatalytic endopeptidase complex;Mus;Nature;Neurodegenerative Disorders;Neuroglia;neuroinflammation;Neurons;neurotoxicity;new therapeutic target;novel;novel therapeutics;old mice;open data;oxidative damage;Oxidative Stress;Pathogenesis;Pathology;Pathway interactions;Peptide/MHC Complex;pharmacologic;Play;Process;protein degradation;Proteins;Proteolysis;Proteome;proteomic signature;Proteomics;receptor;Reporting;response;Role;Senile Plaques;Signal Transduction;single nucleus RNA-sequencing;Stimulus;Synapses;T-Cell Activation;tau aggregation;tau Proteins;Tauopathies;Technology;Testing;Therapeutic;Tissue-Specific Gene Expression;transcriptome;transcriptomics;Transgenic Organisms

PROJECT_TITLE: The Role of Immunoproteasome Function in Alzheimer's Disease and Aging


ORG_CITY: IRVINE

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative  Understanding the aggregation of the β-amyloid peptide to form toxic oligomers is fundamental to understanding the molecular basis of Alzheimer’s disease. This project seeks to understand the structures and biological impacts of these elusive oligomers, through the design, synthesis, and study of synthetic peptides that are based on the β-amyloid peptide and form well-defined oligomers that can be studied in exquisite detail. These studies will advance the field of Alzheimer’s disease research by providing a molecular-level understanding of key species in neurodegeneration and identifying molecular targets for developing diagnostics and therapies.

PI_NAMEs: NOWICK, JAMES S (contact)

PROJECT_TERMS: abeta accumulation;abeta oligomer;Address;Affect;Alzheimer's Disease;Amyloid beta-Protein;analytical ultracentrifugation;Antibodies;Apoptosis;Astrocytes;Biochemical;Biological;Biology;Biophysics;Brain;brain cell;C-terminal;Calcium;Cell Separation;cell type;crosslink;Crystallography;design;Diagnostic;dimer;disulfide bond;endoplasmic reticulum stress;Engineering;Event;experimental study;Fluorescence;Fluorescence Microscopy;Fluorescence Resonance Energy Transfer;Heterogeneity;Homeostasis;Immunologics;immunoreactivity;Inflammatory Response;insight;Knowledge;Laboratories;Length;Link;methyl group;Microglia;Modeling;Molecular;Molecular Sieve Chromatography;Molecular Target;Mus;N-terminal;Necrosis;Nerve Degeneration;Neurites;Neurons;NMR Spectroscopy;Oxidative Stress;Peptide Fragments;Peptides;polyclonal antibody;Positioning Attribute;Property;protein aminoacid sequence;Proteins;Research;Site;Slice;Spectrum Analysis;Structure;synthetic peptide;Tail;tau aggregation;tau-1;uptake;Vertebral column;Visualization;X-Ray Crystallography

PROJECT_TITLE: Structural and Biological Characterization of Diverse Oligomers Derived from Abeta

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);Brain Disorders;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences;Prevention

PHR: PROJECT NARRATIVE Public health relevance. Late onset Alzheimer’s disease (LOAD) is a debilitating neurological disorder affecting the elderly, for which no cure or disease modifying therapy is available yet. We have recently described that microglia, the cell type implicated in LOAD susceptibility by genetic studies, in the human aged brain exists in a variety of functional states and we found one of these microglia phenotypes, named Cluster 7, to be downregulated in AD. Thus, the overarching goal of this proposal is to understand the means through which this microglia subset is involved in healthy aging and AD pathogenesis in humans, in order to provide us with novel microglia centered targets for disease monitoring and potential therapeutic interventions.

PI_NAMEs: OLAH, MARTA  (contact)

PROJECT_TERMS: Acute;Affect;Age;age related changes;age related neurodegeneration;aged;Aging;aging brain;aging population;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease pathology;Alzheimer's disease therapy;Amyloid;Antigen Presentation;Antigen Presentation Pathway;Apoptotic;automated image analysis;Autopsy;Binding;Brain;Brain Pathology;brain tissue;cell type;Cells;Central Nervous System;Characteristics;Clinical;Cluster Analysis;Cognition;Cognitive;cognitive performance;Complex;Coupled;Dementia;density;Development;Diffuse;Disease;Disease Progression;Early identification;Elderly;endophenotype;Enhancers;Environment;Epigenetic Process;epigenetic regulation;experimental study;Female;Future;Genetic;Genetic Predisposition to Disease;genetic signature;Genetic study;Genetic Transcription;genome wide association study;Goals;Haplotypes;healthy aging;Heterogeneity;Homeostasis;Human;Immune;immune function;Immunofluorescence Immunologic;In Situ;In Vitro;Individual;Intervention;Late Onset Alzheimer Disease;Literature;live cell imaging;Maintenance;male;Maps;Masks;Measures;Microglia;Monitor;Names;Nervous System Disorder;Neurodegenerative Disorders;neuronal circuitry;Neurons;novel;Outcome Measure;Pathogenesis;Pathologic Processes;Pathology;Pathway interactions;Persons;Phagocytes;Phagocytosis;Phenotype;Physiological;Physiological Processes;Population;precision medicine;prevent;Preventive;Process;promoter;protein expression;public health relevance;resilience;response;Risk;Role;Senile Plaques;sex;single cell analysis;single cell ATAC-seq;single-cell RNA sequencing;Spatial Distribution;Structure;Surface;Susceptibility Gene;Synapses;Synaptosomes;tau Proteins;Therapeutic;Therapeutic Intervention;Tissues;transcription factor;transcription regulatory network;transcriptomics;Treatment outcome;Undifferentiated

PROJECT_TITLE: Interrogation of a human microglia phenotype associated with Alzheimer's disease


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

PHR: Narrative: Alzheimer’s disease shows distinct progressive histological and behavioral hallmarks but its cell- type basis is not clear. Recent human postmortem studies begin to provide compelling rationale that constituent cell types bear a non-uniform risk profile, but the underlying cell specific progression of vulnerabilities remain unknown. Through cross-disciplinary systems biology approaches we will identify the vulnerable subclass of cells in AD, establish cell-type specific AD signatures and further investigate biological relationship between healthy aging and AD pathology.

PI_NAMEs: PAUL, ANIRBAN  (contact)

PROJECT_TERMS: 3xTg-AD mouse;Adopted;Age;age related;Aging;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Anatomy;Animal Diseases;Architecture;Area;Autopsy;Behavior Control;Behavioral;Bioinformatics;bioinformatics tool;Biological;Blood Vessels;Brain;brain cell;Brain imaging;Brain Mapping;Brain Stem;Categories;Cell Survival;cell type;Cells;Code;Communication;Crows;Cytology;Data;Dementia;density;differential expression;Disease;disease phenotype;Disease Progression;Disparate;entorhinal cortex;Enzymes;excitatory neuron;Fluorescence Microscopy;frontal lobe;Functional disorder;Gene Expression;Gene Family;Genes;genetic makeup;Gliosis;glycosylation;healthy aging;Heparin;Heparitin Sulfate;hippocampal pyramidal neuron;Hippocampus;Histologic;Human;imaging study;Impaired cognition;In Situ;inhibitory neuron;innovation;Interneurons;Knowledge;Label;Late Onset Alzheimer Disease;life span;Light;Measures;Microscopy;Molecular;Morphology;morphometry;Mus;neural circuit;Neurodegenerative Disorders;Neurofibrillary Tangles;Neuroglia;Neurons;novel;Pathologic;Pathology;Pathway interactions;Physiological;postsynaptic;Predisposition;presynaptic;Property;Regimen;resilience;Resolution;response;Risk;Risk Factors;RNA;Sampling;Senile Plaques;sex;single-cell RNA sequencing;Specific qualifier value;Sulfate;sulfurtransferase;survivorship;Synapses;Systems Biology;Taxonomy;Testing;Time;Transcript;transcriptome;transcriptomics;Vulnerable Populations

PROJECT_TITLE: Cell-type specific risk and resilience in Alzheimer’s disease and aging