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

Increased A beta 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 A beta clearance from the brain. In addition, the Wnt/beta-catenin signaling pathway contributes to BBB formation, induction and maturation, and induces BBB function. Dysfunctional Wnt/beta-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. (C) 2014 Elsevier Ltd. All rights reserved.