Novel Cerebrovascular Regulation in Alzheimer’s Disease

About the Research Project
Program
Award Type
Standard
Award Amount
$250,000
Active Dates
July 01, 2013 - June 30, 2016
Grant ID
A2013171S
Acknowledgement
Co-Principal Investigator(s)
Gary Weisman, PhD, University of Missouri
Goals
Alzheimer’s disease (AD) and other neurodegenerative diseases are often preceded by malfunctions in the cerebrovascular system (the brain’s blood vessels), including decreased blood flow in the brain, which leads to hypoxia (low oxygen levels), breakdown of the blood-brain barrier, and, ultimately, to brain atrophy and death. It is known that the endothelial cells that line blood vessels are important regulators of blood flow, and recent work indicates that a protein in endothelial cells (called P2Y2R) is activated under hypoxic conditions, causing relaxation of blood vessels and increases in blood flow. The recent work of Drs. Erb and Weisman with a mouse model of AD shows that global deletion of the P2Y2R (i.e., removal from all cell types) greatly accelerates nerve cell death and the appearance of other classic AD symptoms. Studies in this proposal will investigate whether cerebrovascular changes precede the development of AD symptoms in our AD mouse model, and whether the P2Y2R in endothelial cells, in particular, is important for mediating these events.
Summary
The studies of Drs. Erb and Weisman in this proposal will investigate whether cerebrovascular malfunctions, such as increased levels of hypoxia markers and vascular leakage, precede the development of AD symptoms in their AD mouse model. In particular, they will determine whether the P2Y2R in endothelial cells is important for mediating these events.
If endothelial P2Y2R regulation is substantiated in cerebrovascular function and the progression of AD in the mouse model used by Drs. Erb and Weisman, then this basic research study should provide the basis for specific therapeutic interventions to enhance vascular P2Y2R activity in AD patients, and, ultimately, improve cerebrovascular function and nerve cell survival.
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