# HIV-1 and amyloid beta interactions at the blood-brain barrier

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $472,672

## Abstract

ABSTRACT
The most significant development in HIV epidemiology is the increasing age in the infected
population. Among HIV-associated comorbidities that have been related to aging, neurocognitive
dysfunction and vascular disorders are particularly striking. The current proposal links both
conditions together by focusing on the blood-brain barrier (BBB) and neurogenesis of neural
progenitor cells (NPC).
HIV infected brains are characterized by increased deposition of amyloid beta (Aβ), and we
demonstrated in the previous funding cycle that the BBB (formed primarily by the endothelium of
brain capillaries) actively participates in this process. The current proposal will explore the role of
the brain endothelium-derived extracellular vesicles (ECV) in Aβ transfer to neural progenitor cells
(NPC) and their impaired neurogenesis in HIV-infected brains. The proposed research is built on
the notion that enhanced accumulation of Aβ, toxicity of anti-retroviral therapeutics, and residual
viral replication in HIV-infected brain are driving the brain pathology resulting in neurocognitive
decline. The central hypothesis of the proposal is that Aβ carried by ECV derived from the
brain endothelium enhances HIV infection of NPC and impairs their differentiation into the
neuronal lineage, resulting in neurocognitive decline. Specific mechanisms evaluated in this
application include the impact of Aβ carried by the brain endothelium-derived ECV on HIV
infection and the impaired neurogenesis of NPC (Aim 1), alterations of gap junction-mediated
intercellular communication between infected and non-infected NPC (Aim 2), and (Aim 3) the
contribution of anti-retroviral drugs to amyloid deposition and impaired neurogenesis of NPC in
HIV-infected brain.
Overall, the proposal offers a unique perspective on the interactions between the BBB and Aβ
deposits in a HIV-infected brain, resulting in impaired NPC neurogenesis. We expect that the
project will provide proof-of-principle for the involvement of Aβ in the development of cognitive
dysfunction in HIV.

## Key facts

- **NIH application ID:** 9917817
- **Project number:** 5R01MH072567-13
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Michal Toborek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $472,672
- **Award type:** 5
- **Project period:** 2005-09-20 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917817

## Citation

> US National Institutes of Health, RePORTER application 9917817, HIV-1 and amyloid beta interactions at the blood-brain barrier (5R01MH072567-13). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9917817. Licensed CC0.

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