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

Antonio Currais1, Joshua Goldberg1, Catherine Farrokhi1, Max Chang1, Marguerite Prior1, Richard Dargusch1, Daniel Daugherty1, Aaron Armando2, Oswald Quehenberger2, Pamela Maher1, and David Schubert1
1 The Salk Institute for Biological Studies, La Jolla, CA 92037, USA;
2 Department of Medicine, University of California San Diego, CA 92093-0601, USA.
Key words:
aging, Alzheimer's disease, multiomics, SAMP8 mice, inflammation, J147
09/15/15; Accepted: 10/30/15; Published: 11/11/15


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.