Editorial The Contribution of the Amyloid Hypothesis to the Understanding of Alzheimer’s Disease: A Critical Overview

Copyright © 2012 Laura Morelli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This special issue is devoted to revisit the “amyloid cas-cade hypothesis ” (ACH) in the pathogenesis of sporadic Alzheimer’s disease (AD). Since the identification 20 years ago of the first APP mutation [1] the ACH gained enormous importance based on genetic and biochemical evidence. However the outcome of recent clinical trials aimed at reduc-ing extracellular Aβ levels suggests that such strategy may not have the expected impact on AD progression because the role of Aβ is more complex than that of the lone driver of AD. Some of the reasons proposed for the failure may be the initiation of the trials in demented patients with serious brain damage, and unforeseen serious design flaws in the studies. These results led us to ask whether Aβ play