PROJECT SUMMARY/ ABSTRACT (for Nicholas Hampilos (Ndhlovu): R01 AG063846-01A1 Supplement Application) In this application, we seek a diversity research supplement to the parent award “HARNESSING CELL ALZHEIMER'S SINGLE EPIGENOME-WIDE PROFILING OF MYELOID CELLS TO COMPARE AND CONTRAST FROM HIV-ASSOCIATED COGNITIVE DYSFUNCTION” (AG063846). The parent award seeks to define the epigenomic landscape of myeloid populations in order to differentiate HIV Associated Neurocognitive Disease (HAND) from Mild Cognitive Impairment state of Alzheimer's Disease (MCI-AD) in individuals living with HIV on suppressive antiretroviral therapy (ART). This diversity supplement will expand the scope of research in Specific Aim 2 by enabling the addition of cellular immunophenotyping and MRI and proton magnetic resonance spectroscopy (1H MRS) imaging in 5 subjects with HAND and 5 cognitively normal subjects with HIV from the parent study, with plans to include subjects with MCI-AD in the future if additional funding is secured. The main aims of the supplemental research project are 1) to investigate the neurobiochemical features that may distinguish people living with HIV (PLWH) with HAND versus those without HAND by measuring neurometabolites in the basal ganglia with 1H MRS and 2) to explore possible relationships between neurometabolite levels and monocyte counts and phenotypes by linear regression. With respect to the first aim, our hypothesis is that PLWH with HAND will have lower levels of both GSH and NAA in the basal ganglia compared to PWLH without HAND, reflecting oxidative stress and greater neuronal injury, respectively. We also hypothesize that total and intermediate type monocyte counts as well as CCR2 and CD163 surface expression levels will be inversely correlated with GSH and NAA levels in PLWH, which would further support monocytes being drivers of neuropathology in PLWH. In addition to funding a supplemental research project, the NIA diversity supplement would provide a plethora of mentoring, training, and educational opportunities to Dr. Hampilos at a critical point in his career. More specifically, the diversity supplement would enable Dr. Hampilos to: 1) gain clinical and laboratory research experience in geriatric Neuro HIV and cellular immunology through mentoring, coursework and “hands-on” training in immunophenotyping of peripheral monocytes, which will be required for the proposed supplemental research project, 2) reinforce his radiology training, by enabling Dr. Hampilos to analyze and interpret MRI and 1H MRS results, 3) provide opportunities to enhance his presentation, writing skills, and grantsmanship and 4) generate key preliminary data which would be used to apply for an NIA K22 Career Transition Award and an award from a private foundation in 2024 and/or 2025.