Peripheral clearance of brain-derived Aβ in Alzheimer's disease: pathophysiology and therapeutic perspectives

Alzheimer’s disease(AD)is the most common type of dementia,and no disease-modifying treatments are available to halt or slow its progression.Amyloid-beta(Aβ)is suggested to play a pivotal role in the pathogenesis of AD,and clearance of Aβfrom the brain becomes a main therapeutic strategy for AD.Recent studies found that Aβclearance in the periphery contributes substantially to reducing Aβaccumulation in the brain.Therefore,understanding the mechanism of how Aβis cleared in the periphery is important for the development of effective therapies for AD.In this review,we summarized recent findings on the mechanisms of Aβefflux from the brain to the periphery and discuss where and how the brain-derived Aβis cleared in the periphery.Based on these findings,we propose future strategies to enhance peripheral Aβclearance for the prevention and treatment of AD.This review provides a novel perspective to understand the pathogenesis of AD and develop interventions for this disease from a systemic approach.