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

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $541,772

## Abstract

ABSTRACT
The number of older people living with HIV-1 (PLWH) has increased dramatically in the past
decade in the US and other Western countries. PLWH experience similar health problems as the
general population of older individuals, but at an increased frequency and severity, which is
consistent with accentuated aging. Extensive evidence, including studies in the PI’s laboratory,
demonstrated amyloid pathology in HIV-1 infection, including dysregulations at the blood-brain
barrier (BBB) interface. HIV-infected brains have advanced amyloidopathy, which is characterized
by increased amyloid beta (Aβ) deposition mostly in the perivascular space when compared to
age-matched controls. Among HIV-associated non-AIDS comorbidities, cerebrovascular
diseases, including ischemic stroke, are particularly frequent. While the mechanisms of these
conditions are not fully understood, the present application focuses on the role of enhanced
procoagulant environment and amyloidopathy as critically important underlying factors.
Our current proposal is built on the most exciting and clinically relevant findings resulting from the
previous funding cycle, which explored the role of extracellular vesicles (EV) in Aβ transfer to
neural progenitor cells (NPCs), and their impaired neurogenesis. We mapped EV cargo proteins
and identified Serpine-1 (also known as plasminogen activator inhibitor 1, PAI-1), in various
crossroads of neurodegenerative pathways relevant to HIV-associated neurocognitive decline
(HAND). This is a paramount discovery because Serpine-1 plays a role in both the generation of
a procoagulant environment, and the production and accumulation of Aβ. Therefore, we
hypothesize that a procoagulant environment driven by elevated Serpine-1 levels
contributes to increased risk of ischemic events, delayed post-ischemic recovery, and
enhanced amyloidopathy in HIV-infected brain. Specific mechanisms evaluated in this
application include dysregulation of the BBB and enhanced amyloidopathy (Aim 1), reprograming
mitochondria and induction of inflammatory responses (Aim 2), and impaired differentiation and
migration of NPCs (Aim 3).
The complex role of Serpine-1 in HIV-1 infection in the context of both ischemic events and
amyloidopathy has been overlooked in the literature, making our proposal conceptually novel.
Moreover, this research has potential to generate new therapeutic targets and strategies in aging
and HIV-1 infection, especially in prevention and treatment of cerebrovascular comorbidities,
including ischemic events.

## Key facts

- **NIH application ID:** 10762612
- **Project number:** 2R01MH072567-15
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Michal Toborek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $541,772
- **Award type:** 2
- **Project period:** 2005-09-20 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10762612

## Citation

> US National Institutes of Health, RePORTER application 10762612, HIV-1 and amyloid beta interactions at the blood-brain barrier (2R01MH072567-15). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10762612. Licensed CC0.

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