Vascular hypothesis of Alzheimer’s disease

Abstract

Alzheimer's disease is a progressive neurodegenerative pathology traditionally associated with the accumulation of beta-amyloid and tau proteins. According to the vascular hypothesis, impaired cerebral microcirculation and damage to the blood-brain barrier (BBB) may be the initial mechanisms of the disease. Endothelial dysfunction, capillary atrophy, and BBB leakage lead to insufficient supply of oxygen and nutrients to neurons, allowing toxins to cross the barrier, which then enter the brain. These changes lead to chronic hypoxia, inflammation, neuronal energy deficit, and ultimately neuronal death. The vascular hypothesis offers a new view of Alzheimer's disease as a neurovascular dysfunction that may serve as the basis for new therapeutic approaches.