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

Award Number: R21AG082193
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $191,843 )
2024	2024	UNIVERSITY OF MIAMI	1320 SOUTH DIXIE HIGHWAY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Aging Research	000	2	5/10/2024	NON-COMPETING CONTINUATION	$191,843
														Subtotal = $191,843

Issue Date FY: 2023 ( Subtotal = $242,093 )
2023	2023	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Aging Research	000	1	4/28/2023	NEW	$204,237
2023	2023	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Aging Research	001	1	9/14/2023	NEW	$37,856
														Subtotal = $242,093

Grand Total All Awards = $433,936

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

Award Number: R21AG082193

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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