# Deciphering molecular mechanisms that underlie brain endothelial cell dysfunction with APOE4

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $747,743

## Abstract

Abstract
The neurovasculature plays a key role in homeostasis of the central nervous system. Blood vessels prevent
unwanted molecules from entering the brain while supplying essential nutrients and signaling molecules to meet
the demand of neurons. Specialized brain endothelial cells are the central component of the neurovasculature.
Brain endothelial cells must maintain their own functions while exposed to acute and chronic fluctuations in
circulating molecules from both the brain interstitial fluid and plasma in physiological and pathological states.
Evidence supports that brain endothelial cell dysfunction is a significant pathology in neurodegenerative
disorders and is exacerbated by genetic risk factors. One such factor is APOE genotype, which has long been
linked to neurodegenerative disorders. Compared to APOE3, APOE4 is associated with greater cognitive decline
in aging, poorer outcomes following stroke and traumatic brain injury, and is a major genetic risk factor for
Alzheimer's disease. Several studies, including our own, have identified that one-way APOE4 disrupts neurons
via neurovasculature dysfunction. Therefore, fundamental research identifying cellular mechanisms of how
APOE regulates brain endothelial cell function is important. We have recently identified a new concept that brain
endothelial cell APOE plays a key role in regulating neurovascular function. Supported by our published and
preliminary data, our central hypothesis is brain endothelial cell APOE3 protects the neurovasculature to a
greater extent than APOE4 to maintain behavioral function. Successful data will be significant by identifying a
novel cellular mechanism of how APOE impacts brain function.

## Key facts

- **NIH application ID:** 10879472
- **Project number:** 2R01AG061114-06A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Leon Maing Tai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $747,743
- **Award type:** 2
- **Project period:** 2019-02-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879472

## Citation

> US National Institutes of Health, RePORTER application 10879472, Deciphering molecular mechanisms that underlie brain endothelial cell dysfunction with APOE4 (2R01AG061114-06A1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10879472. Licensed CC0.

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