Research Paper|Volume 7, Issue 11|pp 937—955

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, David Schubert¹

¹The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
²Department of Medicine, University of California San Diego, CA 92093-0601, USA

Received: September 15, 2015Accepted: October 30, 2015Published: November 11, 2015

https://doi.org/10.18632/aging.100838

Copyright: © 2015 Currais et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.