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A comprehensive multiomics approach toward understanding the relationship between aging and dementia


Year of Publication:
Contact PI Name:
David Schubert
Contact PI Affiliation:
The Salk Institute for Biological Studies, La Jolla, California, USA
Antonio Currais, Joshua Goldberg, Catherine Farrokhi, Max Chang, Marguerite Prior, Richard Dargusch, Daniel Daugherty, Aaron Armando, Oswald Quehenberger, Pamela Maher
Primary Reference (PubMED ID):
Funding Source:
Alzheimer's Association
Fritz B. Burns Foundation
Salk Institute Pioneer Fund
National Institute on Aging (NIA)
Study Goal and Principal Findings:

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, J147 could 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.  

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
ATP Synthase F1 Subunit alpha (ATP5F1A)

Animal Model

Model Information:
Model Type:
Accelerated Aging
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Open Field Test
Elevated Plus Maze
Barnes Maze
Object Place Recognition
Activated Astrocytes
Activated Microglia
Synaptic Degeneration
Vascular beta Amyloid Deposits
Amyloid Precursor Protein (APP)
Total Tau Protein
Stress-Activated Protein Kinase (SAPK)
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Activity-Regulated Cytoskeleton-Associated Protein (Arc)
Synapse-Associated Protein 102 (SAP102)
Eukaryotic Translation Initiation Factor 2 alpha (eIF2 alpha)
Heat Shock Proteins
Activated Microglia
Body Weight
Gene Expression Profile-Inflammatory Genes
Whole Transcriptome Analysis