Nonhuman primates (NHPs) are important models of cognitive aging and may be useful for studying risk factors for sporadic late onset Alzheimer?s disease (AD). Their advantages include their biological proximity to humans, and similarity to humans in brain structure and function, and endocrine, social, and cognitive characteristics. Their relatively large brains are favorable for imaging studies and CSF collection and they naturally accumulate brain beta-amyloid (A?) with age that has 100% sequence homology with human A?. In recent years, the vervet has emerged as an important NHP model of AD. Similar to humans, vervets exhibit age-related increases in amyloid burden, neurodegenerative disease biomarkers, synaptic degeneration, histological evidence of tauopathies, changes in tau and A? in cerebrospinal fluid (CSF), and motor and cognitive deficits. These observations suggest that the vervet is a useful model for studying antecedents, mechanisms, biomarkers, and potential therapies for AD. This application seeks supplemental funding to expand the phenotypic characterization and enhance the utilization of the vervet (also known as the African green monkey; Chlorocebus aethiops sabaeus) as a NHP model of Alzheimer?s disease (AD). A major challenge to modeling age-related neuropathology is the assessment of cognitive function in social group-living NHPs. We propose to develop age-sensitive cognitive assessments relevant to the maintenance of independent living, and compare these measures of cognitive capacity to critical AD-related phenotypes including CSF and blood biomarkers, retinal nerve fiber layer thickness via optical coherence tomography, brain volumetrics by magnetic resonance neuroimaging, and physical function. To achieve this goal we propose to study a cohort of group-housed known-age, elderly and middle-aged vervets, housed within their matrilines, in complex, indoor-outdoor enclosures that provide social and physical stimuli that support cognitive, social and physical function. These efforts will combine the unique resources available at the Wake Forest School of Medicine, including the parent grant, the Vervet Research Colony (VRC, P40-OD010965, PI: Matthew Jorgensen), the Alzheimer?s Disease Research Center (ADRC, P30-AG049638, PI: Suzanne Craft) and the Clinical and Translational Science Institute (CTSI, UL1-TR001420, PI: Donald Mcclain). These data will be used in support of proposals of comprehensive, longitudinal assessments of cognitive and physical function in socially housed NHPs relevant to AD risk. These data, images and bio-specimens will be made available to other investigators through the ADRC and CTSI networks.
This supplemental application will support the development of assessments of cognitive capacity in socially housed nonhuman primates (NHPs) that are relevant to Alzheimer?s disease risk and the maintenance of independence late in life, in social group-living elderly and middle-aged vervets, an emerging NHP model of Alzheimer?s disease.
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