Blood-brain barrier integrity in the pathogenesis of Alzheimer's disease

The blood-brain barrier (BBB) tightly controls the molecular exchange between the brain parenchyma and blood. Accumulated evidence from transgenic animal Alzheimer's disease (AD) models and human AD patients have demonstrated that BBB dysfunction is a major player in AD pathology. In this review, we discuss the role of the BBB in maintaining brain integrity and how this is mediated by crosstalk between BBB-associated cells within the neurovascular unit (NVU). We then discuss the role of the NVU, in particular its endothelial cell, pericyte, and glial cell constituents, in AD pathogenesis. The effect of substances released by the neuroendocrine system in modulating BBB function and AD pathogenesis is also discussed. We perform a systematic review of currently available AD treatments specifically targeting pericytes and BBB glial cells. In summary, this review provides a comprehensive overview of BBB dysfunction in AD and a new perspective on the development of therapeutics for AD.