Monday, June 30, 2025 6/30/2025

Endothelial Pannexin1 in Alzheimer’s Disease

Award Number: R21AG075796
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2025

Group Awards By:

View Award Description

Endothelial Pannexin1 in Alzheimer’s Disease - PROJECT SUMMARY/ABSTRACT Alzheimer’s Disease is the most prevalent form of dementia in the elderly and is associated with significantly reduced cerebral blood flow resulting in a chronic state of cerebral hypoperfusion. Patients with Alzheimer’s Disease have increased mortality from ischemic stroke possibly due to preexisting cerebral vascular dysfunction. Thus, it is necessary to examine the mechanisms regulating vascular dysfunction in Alzheimer’s Disease to identify potential therapeutic targets to mitigate cognitive decline and reduce ischemic injury in Alzheimer’s Disease patients. Cerebral arteries become hyperconstrictive in Alzheimer’s Disease and have enhanced responses to nucleotides, such as ATP. Pannexin1 channels in cerebral endothelial cells regulate the release ATP, which subsequently activates downstream purinergic signaling cascades in the vasculature. Pannexin1 protein levels are significantly increased in cerebral tissue from mouse models of Alzheimer’s Disease. We recently discovered that deletion or inhibition of endothelial Pannexin1 reduces cerebral artery myogenic tone to improve cerebral blood flow. In addition to the role in the cerebral arterial vasculature, purinergic signaling is a critical regulator of neuroinflammation in both Alzheimer’s Disease and ischemic stroke. We have also recently demonstrated that deletion of endothelial Pannexin1 profoundly improves post-ischemic stroke infarct volume through a reduction in leukocyte infiltration. Thus, endothelial Pannexin1 is a central regulator of both cerebral arterial vascular tone and post-ischemic stroke inflammation. However, the role of endothelial Pannexin1 in Alzheimer’s Disease and associated ischemic stroke during Alzheimer’s Disease is entirely unknown. We hypothesize that cerebral endothelial Pannexin1 contributes to the development of vascular dysfunction and ischemic stroke severity in Alzheimer’s Disease by increasing vascular tone and inflammation. We will use two aims to test this novel concept. Aim 1 will define the role for endothelial Pannexin1 in regulating cerebral vascular tone and cerebral blood flow during development of Alzheimer’s Disease. Using a mouse model of Alzheimer’s Disease, the APP/PS1 transgenic mice, crossed with our novel transgenic mice conditionally lacking or overexpressing endothelial Pannexin1, we will examine the development of cognitive and biochemical hallmarks of Alzheimer’s Disease and evaluate cerebral arterial myogenic tone and cerebral blood flow. Aim 2 will examine the role of endothelial Pannexin1 in ischemic stroke and neuroinflammation during Alzheimer’s Disease. We will examine ischemic stroke outcome in our transgenic mice with Alzheimer’s Disease, evaluating pre- and post- ischemic stroke neuroinflammation. Successful completion of our study identifying endothelial Panx1 as a novel regulator of cerebral vascular function in Alzheimer’s Disease may provide a target for future therapeutic intervention to improve cognitive function and reduce ischemic stroke injury in Alzheimer’s Disease.


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: 2025 ( Subtotal = $0 )
2025	2022	TUFTS MEDICAL CENTER PARENT, INC.	800 WASHINGTON ST	BOSTON	MA	02111	SUFFOLK	USA	Aging Research	000	1	11/25/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $489,500 )
2022	2022	TUFTS MEDICAL CENTER, INC.	800 WASHINGTON ST	BOSTON	MA	02111	SUFFOLK	USA	Aging Research	000	1	7/22/2022	NEW	$489,500
														Subtotal = $489,500

Grand Total All Awards = $489,500

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Endothelial Pannexin1 in Alzheimer’s Disease

Award Number: R21AG075796

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer