The Vervet Research Colony as Biomedical Resource

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PROJECT SUMMARY Alzheimer’s disease (AD) is the most common neurodegenerative disease causing dementia in the elderly. Vervets/African green monkeys are an excellent nonhuman primate model to study the various pathological changes associated with progression of AD. In recent years, there has been a paradigm shift for the diagnosis of AD using molecular imaging of AD-specific biomarkers via positron emission tomography (PET). Reduction of several biomarkers are implicated in early stages of AD pathogenesis. For example, loss of (a) G-coupled receptor proteins including GPR119 in insulin-triggered regulatory pathways and (b) synaptic density including synaptic vesicle 2A (SV2A) levels are associated with severe cognitive decline processes in the neurological cascade of AD. A key unanswered question is whether the quantitative nature of PET can be used to measure the in vivo concentrations of GPR119 and SV2A in AD. Our goal in this supplement is to develop and validate GPR119 and SV2A as novel imaging biomarkers in a vervet model of AD. In Aim 1, we will develop two potential triazole-based GPR119 agonists and radiolabel them with [11C] and [18F] PET isotopes. GPR119 imaging properties of both the radiotracers will be evaluated in a cohort vervets with variation in age, HbA1c and archived CSF Aβ levels. In Aim 2, we will validate the synaptic density measuring parameters of an established SV2A PET imaging radiotracer, [11C]UCB-J, in the same cohort of vervets from Aim 1. The PET imaging data described here will be used as the basis for a future R01 application that further expands the use of the vervet model of AD.