# Misfolded Protein Aggregates in HIV infection

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $689,684

## Abstract

ABSTRACT
A large number of people living with HIV develop dementia and cognitive dysfunction often referred
as HIV-associated neurocognitive disorder (HAND). The molecular and cellular mechanisms
responsible for HAND are not well understood, but evidence suggests many similarities with
Alzheimer's disease (AD) and related neurodegenerative disorders (NDs). Indeed, various reports
have shown that HIV-infected people develop neuropathological features characteristic of AD,
including deposition of amyloid-beta (Aβ) plaques and neurofibrillary tangles composed by
phosphorylated-Tau (pTau). However, it is unclear whether these abnormalities are associated
specifically with HIV infection and play a role in the neurological abnormalities observed in patients
affected by HAND. A major problem to understand the molecular mechanisms implicated in the
impact of HIV infection in brain degeneration is the lack of appropriate models to study the effect of
HIV in the human brain and the interaction with pathological processes implicated in NDs. The major
goal of this project is to comprehensively study the presence of misfolded protein aggregates in the
brain and biological fluids of HIV-infected people, with or without HAND and also in relationship to
treatment with combination antiretroviral therapy (cART). Our working hypothesis is that HIV
infection or treatment with cART initiates events that promote the misfolding and early
oligomerization of the proteins prone to aggregate in NDs and/or reduces the clearance pathways
that normally eliminate these abnormally folded proteins. To test this hypothesis, we propose the
following specific aims: (1) Detection and characterization of misfolded protein aggregates in the
brain of HIV-infected patients. (2) Detection of misfolded protein aggregates in biological fluids of
HIV-infected patients to attempt development of a biochemical assay to help HAND diagnosis and
monitor its progression. (3) Development of a novel in vitro model to study the effect of HIV infection
in brain alterations using lab-generated brain-like cerebral organoids.
The findings generated in this project may contribute to enlighten the putative role of misfolded
protein aggregates in the neurological abnormalities induced by HIV infection and understand the
potential interaction between AD and related NDs with the pathogenesis of HAND. This project may
also contribute to develop a novel method for biochemical diagnosis of HAND, and relevant model
systems to study the CNS effect of HIV infection.

## Key facts

- **NIH application ID:** 9975672
- **Project number:** 5R01AG061069-03
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** ROBERTO CLAUDIO ARDUINO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $689,684
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975672

## Citation

> US National Institutes of Health, RePORTER application 9975672, Misfolded Protein Aggregates in HIV infection (5R01AG061069-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9975672. Licensed CC0.

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