# Brain capillary Piezo1 ion channels and blood flow regulation in Alzheimer’s Disease

> **NIH NIH R21** · UNIVERSITY OF MIAMI CORAL GABLES · 2024 · $191,843

## Abstract

Summary:
Brain capillary Piezo1 ion channels and blood flow regulation in Alzheimer’s Disease
Brain capillaries are the smallest blood vessels in the brain and are crucial in sensing the metabolic needs of
active neurons and responding to these needs by supplying more blood. Notably, this function is impaired during
neurodegenerative diseases such as Alzheimer’s disease. Not only that capillary sensing is impaired during
Alzheimer’s disease, vascular stiffness and complete disruption of capillary blood flow, referred to as capillary
stalling, have been observed in mouse models of Alzheimer’s disease. Given that capillary stalling disrupts the
hemodynamic forces that capillaries are exposed to, it is important to understand whether Alzheimer’s disease
associates with altered mechano-sensing abilities. We recently discovered that the protein Piezo1 is a
mechanosensor in brain capillaries. Here, we test the overall hypothesis that altered Piezo1 channel activity is
involved in the reduction of brain blood flow in Alzheimer’s disease. We further speculate that tuning Piezo1
activity will improve cerebral blood flow. We will investigate the contribution of endothelial Piezo1 channels to
capillary stalling and blood flow reductions in a mouse model of Alzheimer’s disease. Using capillary endothelial
cells from wild-type and Alzheimer’s disease mice, we will employ innovative electrophysiological and molecular
approaches to assess whether Piezo1 ion channel expression and function are altered during Alzheimer’s
disease. In the second aim, we will utilize in vivo high-resolution, two-photon microscopy to investigate capillary
stalling and blood flow changes in Alzheimer’s disease mice while pharmacologically manipulating Piezo1
channels. This novel work could lead to new therapeutic strategies not previously tested.

## Key facts

- **NIH application ID:** 10834269
- **Project number:** 5R21AG082193-02
- **Recipient organization:** UNIVERSITY OF MIAMI CORAL GABLES
- **Principal Investigator:** Oliver Bracko
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $191,843
- **Award type:** 5
- **Project period:** 2023-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834269

## Citation

> US National Institutes of Health, RePORTER application 10834269, Brain capillary Piezo1 ion channels and blood flow regulation in Alzheimer’s Disease (5R21AG082193-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10834269. Licensed CC0.

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