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 (A beta) is suggested to play a pivotal role in the pathogenesis of AD, and clearance of A beta from the brain becomes a main therapeutic strategy for AD. Recent studies found that A beta clearance in the periphery contributes substantially to reducing A beta accumulation in the brain. Therefore, understanding the mechanism of how A beta is 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 A beta efflux from the brain to the periphery and discuss where and how the brain-derived A beta is cleared in the periphery. Based on these findings, we propose future strategies to enhance peripheral A beta clearance 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.