# Immune Mechanisms Underlying Age-Related Neurodegeneration in HIV Infection

> **NIH NIH RF1** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $391,655

## Abstract

Project Summary
As the leading cause of age-related disabilities, neurocognitive diseases such as Alzheimer’s disease (AD) and
other dementias are poised to significantly impact global health care as the population of people aged 60 and
older nearly doubles in the next three decades. One group at a significantly greater risk of age-related
neurodegenerative diseases are HIV-infected (HIV+) patients. An estimated 50% of HIV+ patients on
antiretroviral therapy (ART) develop mild to severe impairments in brain function with age. Designated as HIV-
associated neurocognitive disorders (HAND), this syndrome is expected to increase dramatically in the next
decade as more than 70% of Americans with HIV turn 50 and older, and ART becomes more widely available in
the developing world. The imminent global impact of HAND underscores the urgent need to understand
the mechanistic basis of neurodegeneration in HIV+ patients on ART and devise effective interventions.
This proposal is focused on understanding the immune mechanisms underlying age-related neurodegeneration
following HIV infection using a robust rhesus model which recapitulates salient aspects of HIV pathophysiology
in humans. In Aim 1 of this research project, we will establish the role of monocytes in neurodegeneration;
specifically, pro-inflammatory monocytes. In Aim 2, we will determine the role of Th1, and Th17 CD4 T cell subsets
in neurodegeneration. Considering that HIV and HIV-associated neuroinflammation interfere with amyloid and
tau metabolism, in Aim 3 we will investigate whether pathological AD markers are induced during HIV-associated
neuroinflammation. The collective complementary expertise of the investigators and collaborators in tackling the
scientific questions posed in the application will facilitate an in-depth understanding of the immune and synaptic
mechanisms underlying neurodegeneration. These preclinical studies will establish the mechanistic and
experimental foundations to identify predictive biomarkers of HAND and subsequently enable opportunities in a
relevant and tractable model for testing novel, targeted interventions as adjunctive therapy to ART. Only by
quantifying measures of SIV-induced HAND sequelae in macaques can parameters of intervention be evaluated
for efficacy prior to human studies.

## Key facts

- **NIH application ID:** 10094931
- **Project number:** 3RF1AG061001-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Swaminathan Smita Iyer
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,655
- **Award type:** 3
- **Project period:** 2018-09-30 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10094931

## Citation

> US National Institutes of Health, RePORTER application 10094931, Immune Mechanisms Underlying Age-Related Neurodegeneration in HIV Infection (3RF1AG061001-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10094931. Licensed CC0.

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