"Unexpectedly Stalled - Uncovering the Cause and Consequences of Brain Blood Flow Deficits in Mouse Models of Alzheimer's Disease"

Dr. Chris B. Schaffer
Associate Biomedical Engineering Professor
Cornell University, Ithaca, NY

Blood flow to the brain is reduced by about one-third in patients with Alzheimer’s disease. This decreased flow contributes to the memory and cognitive problems seen in Alzheimer’s and may accelerate progression of the disease. The mechanism causing this poor brain blood flow, however, has remained undiscovered. Using high-resolution in vivo imaging of blood flow in mouse models of Alzheimer’s disease, we have identified capillary segment plugging by firmly adhered white blood cells as a mechanism that contributes to this blood flow decrease. In Alzheimer’s mice, nearly 2 percent of capillaries have stalled blood flow due to an adhered leukocyte, while wild mice have stalls in less than 0.5 percent of capillaries. Because one stalled capillary decreases blood flow in many downstream branches, the 2 percent of capillaries stalled leads to substantial blood flow decreases. When we blocked leukocyte adhesion, cortical blood flow increased by about 30 percent. This increase in brain blood flow was accompanied by an immediate improvement in cognitive performance of mice concerning spatial and working memory tasks. These data suggest that white blood cells sticking in capillaries may be responsible for the reduced blood flow to the brain seen in Alzheimer’s patients and that treating this could both improve cognitive function and slow disease progression.

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