# Comparative Study of Molecular Signatures in HIV-Related Neuropathogenesis and Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $787,498

## Abstract

Abstract
Problem. The use of combination antiretroviral therapy (cART) has allowed people living with HIV (PLWH) to
live longer and healthier. Nevertheless, more than half of PLWH still have varying degrees of HIV Associated
Neurocognitive Disorder (HAND) despite viral suppression with cART. Longer duration of HIV infection and
aging may have conjoining negative effects on cognitive function and neurodegeneration. As the PLWH are
growing older, it is important to differentiate HAND from neurodegenerative diseases affecting the general
aging population, such as Alzheimer's Disease (AD). Both HAND and AD might share neuropathological
mechanisms, which have not been systematically studied, in PLWH during suppressive cART.
Overarching Goal. To characterize the molecular signatures underlying HAND during viral suppression on
cART, and describe the commonalities and differences with those molecular signatures associated with AD.
Cohorts and Samples. We will use complementary and well-characterized cohorts with extensive longitudinal
available clinical, neurocognitive and laboratory data from two major research programs: HIV Neurobehavioral
Research Program (HNRP) and Shiley-Marcos Alzheimer's Disease Research Center (ADRC).
A. HNRP: We will retrospectively include CSF and blood samples from participants who (i) had normal
cognition at baseline and had incident HAND at a subsequent time-points (HAND group, n=100) and, (ii) age-
matched participants who had normal cognition at baseline and did not develop HAND in any of the
subsequent time-points (no-HAND group, n=100). For the HAND group, we will also evaluate samples at the
time-point when HAND was first diagnosed. For subset of participants (n=20), we will include stored post-
mortem brain tissue for exploratory evaluation.
B. ADRC: We will retrospectively include CSF and blood samples from participants who: (i) had Mild
Neurocognitive Impairment (MCI) at baseline and developed AD in the subsequent time-point (AD group,
n=50) and, (ii) age-matched participants who had normal cognition during all observational time-points (control
group, n=50). Brain tissue will also be available for a subset of participants (n=20) for exploratory evaluation.
Approach. We propose a highly innovative approach by generating and analyzing high dimensional data
focused on study objectives designed to be responsive to the parent RFA-AG-18-023. Specifically, we will
generate metabolomics and lipidomics (aim 1), transcriptomics (aim 2), and we will integrate these data with
relevant AD-associated genetic variants, clinical variables and measures of classical AD biomarkers (aim 3) to
develop molecular interaction networks and predictive models of HAND and AD. Our study has the potential to
yield highly translatable results by identifying pathways that can be targeted to improve care for both ageing
HIV population and AD population. The data collected as part of this project will also lay the groundwork for
future studies that ...

## Key facts

- **NIH application ID:** 9928390
- **Project number:** 5R01AG061066-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Michelli Faria de Oliveira
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $787,498
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928390

## Citation

> US National Institutes of Health, RePORTER application 9928390, Comparative Study of Molecular Signatures in HIV-Related Neuropathogenesis and Alzheimer's Disease (5R01AG061066-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9928390. Licensed CC0.

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