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