Figure 3.

Proposed model for BBB dysfunction in AD pathogenesis. Dysregulation of the neurovascular unit (e.g., diminished endothelial transport, loss of tight junction (TJ) integrity, basement membrane disorganization, pericyte degeneration, and astrocyte depolarization) is induced during Alzheimer’s disease (AD) progression, which is particularly associated with brain Aβ accumulation. These alterations, in turn, contribute directly or indirectly to the disturbed Aβ clearance in the neurovascular unit and across the BBB, thus setting up a vicious cycle in AD pathogenesis. In parallel, plasma protein leakage, reduced brain glucose uptake, and neuroinflammation caused by BBB damage may lead to further cellular toxicity, making neurons more susceptible to AD pathologies.