CSF1R Signaling in Age-Related HIV Neurodegeneration

Eastern Virginia Medical School, Norfolk VA

Investigators

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Abstract

Project Summary Despite the advent of highly active antiretroviral therapy, HIV-associated neurocognitive disorders (HAND) remain surprisingly common. As treated HIV patients have been living longer, the HIV-infected population is aging rapidly. Since older age (>50 years old) is a major risk factor for HAND, there is a growing concern about the possibility of a much greater prevalence of HAND in the next few decades in the United States and globally. Moreover, aging HIV patients are now also facing a new risk of developing Alzheimer’s disease (AD). All these (the aging HIV population with an alarming prevalence of HAND in the absence of effective treatment and the possibility of an impending epidemic of AD, HAND or combination) highlight the urgent need for greater understanding of the pathogenesis of this disease. The principal challenge in HAND and AD research is a paucity of clinically more relevant animal models to study the mechanisms of pathogenesis and evaluate therapeutics. The overall goal of this supplement is to determine if aging rhesus macaques with SIV+ART that are undergoing accelerated aging, develop neuroinflammation and brain lesions suggestive of AD-like disease processes. The significance of this supplement is that if overlapping pathways in inflammatory or AD-related biomarkers and similar lesions are observed, this would contribute to hypothesis-driven proposal for validation of related mechanisms between SIV/HIV and AD disease, new model development for AD, and identification of converging pathways of pathogenesis for identifying targets of intervention.