2021 Alzheimer's Association Research Grant (AARG)

Improving Glymphatic and Microvascular Function in Alzheimer's disease

How are the processes of blood flow and waste removal in the brain impacted by Alzheimer’s?

Paulo Pires, Ph.D.
University of Arizona
Tucson, AZ - United States

Background

Beta-amyloid and tau accumulate to form plaques and tangles respectively, the two hallmark brain changes observed in Alzheimer's. Beta-amyloid can accumulate near brain blood vessels, and is associated with increased stiffening of the vessels. When vessels are stiffer, it can be difficult for surrounding muscle cells to properly pump blood and this can restrict the blood flow throughout the brain. This process is known as “cerebral amyloid angiopathy” or CAA. 
 
CAA is thought to negatively impact brain function in two ways. One, the restriction of blood flow to the brain starves active brain cells of vital nutrients and impairs their function. Two, CAA reduces the efficiency of the brain’s waste removal system, known as the glymphatic system. Without a functional system to deliver nutrients and remove waste, brain cells may eventually die, leading to cognitive decline.
 

Research Plan

Dr. Paulo Pires and his team will study if they can improve blood flow and waste removal in the brains of genetically engineered Alzheimer’s-like mice. The researchers will use gene therapy to target specific cells of the brain’s blood vessels and enhance blood flow/nutrient delivery and improve waste removal/glymphatic flow. Dr. Pires and his colleagues will study if these improvements impact the rate of cognitive decline in genetically engineered Alzheimer’s-like mice, as well as investigate the underlying biologic mechanisms.

Impact

The results may expand the understanding of how Alzheimer’s impacts blood flow and waste removal in the brain. If successful, the findings may help identify new targets for therapies aimed at slowing the progression of Alzheimer’s and other dementias.