VEGF Paradoxically Reduces Cerebral Blood Flow in Alzheimer's Disease Mice.

Vascular dysfunction plays a critical role in the development of Alzheimer's disease. Cerebral blood flow reductions of 10% to 25% present early in disease pathogenesis. Vascular Endothelial Growth Factor-A (VEGF-A) drives angiogenesis, which typically addresses blood flow reductions and global hypoxia. However, recent evidence suggests aberrant VEGF-A signaling in Alzheimer's disease may undermine its physiological angiogenic function. Instead of improving cerebral blood flow, VEGF-A contributes to brain capillary stalls and blood flow reductions, likely accelerating cognitive decline. In this commentary, we explore the evidence for pathological VEGF signaling in Alzheimer's disease, and discuss its implications for disease therapy.