Clearing the amyloid in Alzheimer's: progress towards earlier diagnosis and effective treatments – an update for clinicians

Abstract

SUMMARY  A beta (Aβ or β-amyloid) is a key molecule in Alzheimer's disease (AD) pathogenesis. According to the ‘amyloid hypothesis’, the gradual accumulation of Aβ triggers events which results in neuronal loss in regions of the brain involved with memory and learning. Diverse agents have been developed to reduce brain Aβ accumulation or to enhance its clearance. Some have progressed to human trials, however all have failed to improve cognition in patients. This has led researchers to question whether Aβ is really the problem. However, the trials have been targeting end stages of AD, by which stage extensive irreversible neuronal damage has already occurred. Intervention is required preclinically, therefore preclinical AD biomarkers are needed. In this regard, amyloid imaging and cerebrospinal fluid biomarkers are leading the way, with plasma biomarkers and eye tests also being investigated. This review covers the current state of knowledge of Aβ as an early diagnostic biomarker and as a therapeutic target in AD.