The Vervet Research Colony as Biomedical Resource

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PROJECT SUMMARY Vervet monkeys (Chlorocebus aethiops sabaeus) develop age-related amyloid pathology that resembles very early stages of Alzheimer's disease in humans. Hippocampal hypometabolism and volume reduction occur in amnestic mild cognitive impairment in humans, a condition characterized by impaired everyday memory which often precedes development of Alzheimer's disease, but the effect of age on hippocampal function in vervets is not known. Determining how age and Alzheimer's-related biomarkers are associated with hippocampal structure and function in vervets would dramatically enhance the utility of this species as a model for age- related cognitive impairments and early-stage Alzheimer's disease. As a first, exploratory step towards characterizing hippocampal structure and function in aging vervets, the goal of this application is to develop a continuous tracking system to monitor locomotor behavior in group-housed vervets in the Vervet Research Colony at Wake Forest. This will allow us to monitor position within the home environment longitudinally for long periods of time (weeks to months) and will allow us to determine whether locomotor behavior in aging vervets displays patterns characteristic of dementia-associated "wandering" in humans. We will also measure hippocampal volume with structural MRI and metabolic activity with FDG-PET imaging, and Alzheimer's- related blood biomarkers. This will allow us to explore whether any features of movement around the home enclosure discriminate between individuals based on hippocampal volume, glucose metabolic rate, or fluid biomarkers of Alzheimer's disease. Because behavioral readouts of hippocampal function currently are mainly obtained through prolonged cognitive testing, which is resource-intensive and impractical to apply across large groups of primates, this proposal has the potential to uncover behavioral measures that can be continuously acquired and analyzed in real time and over a period of months to years that signal hippocampal dysfunction with aging and neuropathology in vervet monkeys. This will open new possibilities for using this model species to study interventions that may offset the development of Alzheimer's pathology in humans during the earliest phases of the disease.