Nature Reviews Drug Discovery 10, 698-712 (September 2011) | doi:10.1038/nrd3505

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

Eric Karran1, Marc Mercken1 & Bart De Strooper2  About the authors


The amyloid cascade hypothesis, which posits that the deposition of the amyloid-β peptide in the brain is a central event in Alzheimer's disease pathology, has dominated research for the past twenty years. Several therapeutics that were purported to reduce amyloid-β production or aggregation have failed in Phase III clinical testing, and many others are in various stages of development. Therefore, it is timely to review the science underpinning the amyloid cascade hypothesis, consider what type of clinical trials will constitute a valid test of this hypothesis and explore whether amyloid-β-directed therapeutics will provide the medicines that are urgently needed by society for treating this devastating disease.

Author affiliations

  1. Janssen Research and Development, Neuroscience Therapeutic Area, Turnhoutseweg 30, 2340 Beerse, Belgium.
  2. Flanders Institute for Biotechnology (VIB), Department of Molecular and Developmental Genetics, Katholieke Universiteit Leuven, Gasthuisberg Herestraat 49, Box 6023000 Leuven, Belgium.

Correspondence to: Eric Karran1 Email:

Published online 19 August 2011

Additional data