# Sexual Dimorphism in Cerebral Amyloid Angiopathy and Vascular Dementia: Investigating the Role of Fibrinolytic System

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $195,000

## Abstract

PROJECT SUMMARY/ ABSTRACT
Cerebral amyloid angiopathy (CAA) is an Alzheimer's disease related dementia (ADRD). The
deposition of amyloid around the blood vessels in the brain leads to CAA. CAA is characterized
by small cortical microbleeds in the brain, which not only leads to devastating spontaneous
intracerebral hemorrhages, but also contributes to vascular dementia in the elderly. Therefore,
this disease has a high mortality and disability burden. Interestingly, Alzheimer's disease (AD), a
disease in which amyloid deposits are found predominantly in the brain parenchyma rather than
the cerebral blood vessels, has been increasingly recognized as a sexually dimorphic disease.
In AD patients, women perform poorly on verbal memory tasks and have a faster cognitive
decline compared to men. However, such differences are understudied in CAA, which shares a
very similar disease pathology of amyloid deposition. Using mouse models of CAA, we will study
potential sex differences in CAA across the lifespan. We will do this by studying cognition, MRI
and amyloid burden in the brain at different ages. The goal is to understand the complex
interactions of sex and age in CAA progression.
Like in many other diseases, the mechanism of CAA pathology may differ in males and females.
The fibrinolytic pathway is known to be involved in the clearance of amyloid in Alzheimer's
disease. We have found this pathway is sexually dimorphic. Our focus will initially be on
Plasminogen Activator Inhibitor 1 (PAI-1), which is an inhibitor of tissue plasminogen activator
that activates plasminogen and assists in amyloid clearance. In this proposal, we will use
pharmacological inhibition and mice with genetic deletion of PAI-1 to determine if PAI-1 is a
viable sex specific drug target for CAA. This study aims to fill the gap in our understanding of
the sexual dichotomies in CAA pathology and vascular dementia and assist in development of
sex specific therapies.

## Key facts

- **NIH application ID:** 10463801
- **Project number:** 5R21AG070860-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Bharti Manwani
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $195,000
- **Award type:** 5
- **Project period:** 2021-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463801

## Citation

> US National Institutes of Health, RePORTER application 10463801, Sexual Dimorphism in Cerebral Amyloid Angiopathy and Vascular Dementia: Investigating the Role of Fibrinolytic System (5R21AG070860-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10463801. Licensed CC0.

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