Brain Pericytes and the Progression of Alzheimer's Disease

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To sustain the health of tissues in the body, the circulatory system needs to efficiently and continuously supply O2 and nutrients to every living cell in the brain, while also removing metabolic waste. Dr. Gonzales’s current work focuses on contractile pericytes located at capillary junctions and their role in regulating capillary blood flow. Contractile pericytes have multiple projections that wrap around capillaries and can regulate the passage of red blood cells (RBCs), but unlike bona fide arterial smooth muscle cells, a single pericyte is capable of compartmentalized contraction and constriction of different branches of a capillary junction. Dr. Gonzales’s recent work describes how pericytes play an important and novel role in structurally and dynamically modulating the shape of capillary junctions to insure the proper distribution of RBCs within the capillary network. The current proposal will test the hypothesis that amyloid-β, the major constituent of plaques in Alzheimer’s disease and cerebral amyloid angiopathy, disrupts or “short circuits” pericyte Ca2+ dynamics, leading to the eventual loss of junctional pericytes and an exponential decline in capillary perfusion efficiency, ultimately resulting in neuronal cell death.