Clearance of amyloid-beta in Alzheimer's disease: progress, problems and perspectives

Alzheimer's disease (AD) is the most common form of senile dementia and the fourth highest cause of disability and death in the elderly. Amyloid-beta (A beta) has been widely implicated in the etiology of AD. Several mechanisms have been proposed for A beta clearance, including receptor-mediated A beta transport across the blood-brain barrier and enzyme-mediated A beta degradation. Moreover, pre-existing immune responses to A beta might also be involved in A beta clearance. In AD, such mechanisms appear to have become impaired. Recently, therapeutic approaches for A beta clearance, targeting immunotherapy and molecules binding A beta, have been developed. In this review, we discuss recent progress and problems with respect to A beta clearance mechanisms and propose strategies for the development of therapeutics targeting A beta clearance.