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

Abstract

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 (Abeta) has been widely implicated in the etiology of AD. Several mechanisms have been proposed for Abeta clearance, including receptor-mediated Abeta transport across the blood-brain barrier and enzyme-mediated Abeta degradation. Moreover, pre-existing immune responses to Abeta might also be involved in Abeta clearance. In AD, such mechanisms appear to have become impaired. Recently, therapeutic approaches for Abeta clearance, targeting immunotherapy and molecules binding Abeta, have been developed. In this review, we discuss recent progress and problems with respect to Abeta clearance mechanisms and propose strategies for the development of therapeutics targeting Abeta clearance.