Squirrel Monkey Breeding and Research Resource – Administrative Supplement (Brain and Genomic Resource Development)

University Of Tx Md Anderson Can Ctr, Houston TX

Investigators

Linked publications, trials & patents

Abstract

Project Summary Alzheimer’s disease (AD) is a major health concern defined by pathologic changes in the brain that coincide with altered behavior and cognitive function. Many have suggested that there is a need for primate models of AD because they naturally recapitulate some neuropathological features of AD with advanced age whereas other model organisms do not (i.e., rodents). For instance, while amyloid-beta (Aβ) deposition occurs in most mammals, tau-positive neurofibrillary tangles (NFT) have only been identified in a few nonhuman species studied to date. Additionally, elderly nonhuman primates, develop cerebral amyloid angiopathy (CAA), a neurovascular condition found in 80% of AD patients and associated with cognitive decline. Here, we are requesting supplemental funding to further develop the squirrel monkey model for use in research on cognitive aging and the development of CAA and related AD pathology. In Aim 1, we propose to perform whole genome sequencing (WGS) in a sample of 140 squirrel monkeys. The selection of animals will be based on two factors: a) previous knowledge that individuals are descendants of animals with known AD-related phenotypes, and b) efforts to maximize the future utility of the information obtained by sequencing breeding animals that are producing the next generations of colony animals. The WGS data will be made publicly available to the scientific community and will used to perform preliminary analyses of association with cognitive phenotypes and biomarkers currently being obtained in this same cohort of monkeys. In Aim 2, we propose to prospectively develop a systematic collection program to obtain frozen and fixed brain materials form the squirrel monkey population. This program will be modeled after existing postmortem brain programs and will allow for harmonization in the curation and storage methods across multiple species used in comparative studies of aging and AD pathology.