title: A comprehensive multiomics approach toward understanding the relationship between aging and dementia.
abstract: Because age is the greatest risk factor for sporadic Alzheimer's disease (AD), phenotypic screens based upon old age-associated brain toxicities were used to develop the potent neurotrophic drug J147. Since certain aspects of aging may be primary cause of AD, we hypothesized that J147 would be effective against AD-associated pathology in rapidly aging SAMP8 mice and could be used to identify some of the molecular contributions of aging to AD. An inclusive and integrative multiomics approach was used to investigate protein and gene expression, metabolite levels, and cognition in old and young SAMP8 mice. J147 reduced cognitive deficits in old SAMP8 mice, while restoring multiple molecular markers associated with human AD, vascular pathology, impaired synaptic function, and inflammation to those approaching the young phenotype. The extensive assays used in this study identified a subset of molecular changes associated with aging that may be necessary for the development of AD.
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Currais
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Goldberg
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Farrokhi
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Chang
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Prior
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Dargusch
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Daugherty
authors.affiliation: Department of Medicine, University of California San Diego, CA 92093-0601, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Armando
authors.affiliation: Department of Medicine, University of California San Diego, CA 92093-0601, USA.
authors.forename: Oswald
authors.initials: O
authors.lastname: Quehenberger
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Maher
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: David
authors.initials: D
authors.lastname: Schubert
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology*; D016229:Amyloid beta-Peptides / Q000032:analysis; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier; D015777:Eicosanoids / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D018782:Maze Learning / Q000187:drug effects; D055432:Metabolomics; D051379:Mice; D059467:Transcriptome
chemical_list: D016229:Amyloid beta-Peptides; D015777:Eicosanoids; D048031:JNK Mitogen-Activated Protein Kinases; D005978:Glutathione
keywords: Alzheimer's disease; J147; SAMP8 mice; aging; inflammation; multiomics