Alzheimer's Gene Triggers Early Breakdowns in Blood-Brain Barrier, Predicting Cognitive Decline

A study by University of Southern California (USC) researchers in Nature sheds light on how the Alzheimer's disease gene APOE4 triggers leakage in the blood-brain barrier, reports USC News . "Severe damage to vascular cells called pericytes was linked to more severe cognitive problems in APOE4 carriers," said USC's Berislav Zlokovic. "APOE4 seems to speed up the breakdown of the blood-brain barrier by activating an inflammatory pathway in blood vessels, which is associated with pericyte injury." Using a combination of standard memory tests and advanced neuroimaging, the researchers found damaged capillaries in the brain's memory center, the hippocampus, and medial temporal lobe in APOE4 carriers. This damage corresponded with elevated levels of the inflammatory protein cyclophilin A, which is an early sign of the disease in people already at higher risk of Alzheimer's. The findings suggest that a potential treatment could focus on these capillaries.