# Alzheimer's associated neuropathology; Risk modification by alcohol in antiretroviral-treated SIV-infected rhesus macaques

> **NIH NIH P60** · LSU HEALTH SCIENCES CENTER · 2021 · $367,500

## Abstract

Abstract
The longevity of persons living with HIV (PLWH) has been prolonged with the use of antiretroviral therapy (ART).
Age-related complications, especially cognitive deficits, rise as PLWH live longer. Even in the post-ART era,
neurocognitive deficits remain prevalent in PLWH. HIV-associated neurocognitive disorder (HAND) and co-
occurring alcohol use disorder (AUD) can exacerbate these deficits. HAND persists despite the widespread
implementation of ART, and as PLWH age on ART regimens, the risk of age-related comorbidities such as
Alzheimer's disease (AD) may increase. Previously, we showed that chronic binge alcohol (CBA) administration
prior to and during simian immunodeficiency virus (SIV) infection in rhesus macaques unmasks learning deficits
in operant learning and memory tasks. Furthermore, exploratory analysis of CBA-induced differential expression
of hippocampal genes revealed a dysregulation of genes involved in inflammation, immune responses, and
neurotrophic support. Various mechanisms including neuroinflammation induced by HIV proteins (e.g., Tat,
gp120, Nef), excitotoxicity, oxidative stress, and exposure to ART could contribute to the deposition of beta-
amyloid (Aβ) and phosphorylated-tau (p-tau) proteins associated with AD. Importantly, neuron-derived
extracellular vesicles (NDEVs) from AD subjects may serve as a readily accessible AD biomarker as they contain
increased levels of soluble Aβ1-42, amyloid precursor protein, and hyperphosphorylated tau. Pathogenic
substances and genetic cargo packaged in NDEVs can also interact with local microglia leading to further
pathophysiological changes. Alcohol increases NDEV biogenesis and increases specific subsets of microRNAs
and protein content in NDEVs. This application will identify whether NDEVs derived from CBA-administered,
SIV-infected animals contain protein cargo indicative of AD pathology. Our overarching hypothesis is that CBA
and prolonged exposure to SIV/ART in rhesus macaques additively produce neuroadaptations and associated
biomarkers that may increase the risk for AD.

## Key facts

- **NIH application ID:** 10299829
- **Project number:** 3P60AA009803-28S1
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** PATRICIA E. MOLINA
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $367,500
- **Award type:** 3
- **Project period:** 1996-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10299829

## Citation

> US National Institutes of Health, RePORTER application 10299829, Alzheimer's associated neuropathology; Risk modification by alcohol in antiretroviral-treated SIV-infected rhesus macaques (3P60AA009803-28S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10299829. Licensed CC0.

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