Discerning the Role of Blood Brain Barrier Dysfunction in Alzheimer's Disease

Alzheimer's disease (AD) is the most common form of neurodegenerative disease. The predominant characteristics of AD are the accumulation of amyloid-β (Aβ) and hyperphosphorylated tau in the brain. Blood brain barrier (BBB) dysfunction as one of the causative factors of cognitive impairment is increasingly recognized in the last decades. However, the role of BBB dysfunction in AD pathogenesis is still not fully understood. It remains elusive whether BBB dysfunction is a consequence or causative fact of Aβ pathology, tau pathology, neuroinflammation, or other conditions. In this review, we summarized the major findings of BBB dysfunction in AD and the reciprocal relationships between BBB dysfunction, Aβ pathology, tau pathology, and neuroinflammation. In addition, the implications of BBB dysfunction in AD for delivering therapeutic drugs were presented. Finally, we discussed how to better determine the underlying mechanisms between BBB dysfunction and AD, as well as how to explore new therapies for BBB regulation to treat AD in the future.