Dysfunctional Wnt/β-catenin signaling contributes to blood–brain barrier breakdown in Alzheimer’s disease

•Increasing Aβ clearance from brain is an important method to attenuating Alzheimer’s disease (AD).•The blood–brain barrier (BBB) plays a critical role in Aβ clearance from brain.•The dysfunction of Wnt/β-catenin signaling contributes to the BBB breakdown and the progress of AD.•The potential of the Wnt/β-catenin signaling acting as therapeutic approaches for AD is discussed here.

Increased Aβ clearance from brain is essential for restoring the pathological manifestation of Alzheimer’s disease (AD) and attenuating the cognitive disorder. The blood–brain barrier (BBB) plays a critical role in maintaining homeostasis of the brain, and transporters e.g. P-glycoprotein (P-gp) are essential for Aβ clearance from the brain. In addition, the Wnt/β-catenin signaling pathway contributes to BBB formation, induction and maturation, and induces BBB function. Dysfunctional Wnt/β-catenin signaling in the BBB reveals the importance of this pathway, since this contributes to the neurodegeneration characteristic of AD. Based on the above evidence, we propose that targeting the canonical Wnt signaling pathway could be promising therapeutic approach for treatment of AD.