Hemodynamic Consequences of Deformed Microvessels in the Brain in Alzheimer's Disease

The cause of sporadic Alzheimer's disease (AD) remains a mystery. Mounting clinical and experimental data, however, suggest that a cerebral hemodynamic role may affect neuronoglial metabolism. Light and electron microscopy have consistently revealed that the microvasculature in AD brains contains structurally deformed capillaries which create a distorted intraluminal conduit for blood flow. The cerebral capillary distortions can create "disturbed" rather than "laminar" blood flow. Chronically disturbed capillary blood flow will impair normal delivery of essential nutrients to brain neurons as well as impede catabolic outflow of CNS waste products. This condition will negatively affect cerebral metabolism, primarily because of impaired glucose delivery to neurons. Impaired glucose delivery to AD brain results in a patho-chemical cascade that will impair the Na+, K(+)-ATPase ion pump and affect the syntheses of ATP, acetylcholine, and other neurotransmitters. The outcome of this metabolic dysfunction can promote neurofibrillary tangle and senile plaque formation in AD brain.