The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics.

The amyloidcascade hypothesis — which posits that the deposition of the amyloid-β peptide in the brain is a central event in Alzheimer's disease (AD) pathology — has strongly influenced recent AD drug discoveryefforts. However, so far all agents targeting amyloid-β have failed in Phase III trials. Here, Karran and colleagues re-evaluate the amyloidcascade hypothesis and explore the future potential of amyloid-β-targeting therapeutics.