title: The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics.
abstract: 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.
authors.affiliation: Janssen Research and Development, Neuroscience Therapeutic Area, Turnhoutseweg 30, 2340 Beerse, Belgium. eric.karran@gmail. com
authors.forename: Eric
authors.initials: E
authors.lastname: Karran
authors.forename: Marc
authors.initials: M
authors.lastname: Mercken
authors.forename: Bart
authors.initials: B
authors.lastname: De Strooper
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D006801:Humans; D058225:Plaque, Amyloid / Q000473:pathology / Q000517:prevention & control; D012107:Research Design; D017211:Treatment Failure
chemical_list: D016229:Amyloid beta-Peptides