title: The case for rejecting the amyloid cascade hypothesis.
abstract: Alzheimer's disease (AD) is a biologically complex neurodegenerative dementia. Nearly 20 years ago, with the combination of observations from biochemistry, neuropathology and genetics, a compelling hypothesis known as the amyloid cascade hypothesis was formulated. The core of this hypothesis is that it is pathological accumulations of amyloid-β, a peptide fragment of a membrane protein called amyloid precursor protein, that act as the root cause of AD and initiate its pathogenesis. Yet, with the passage of time, growing amounts of data have accumulated that are inconsistent with the basically linear structure of this hypothesis. And while there is fear in the field over the consequences of rejecting it outright, clinging to an inaccurate disease model is the option we should fear most. This Perspective explores the proposition that we are over-reliant on amyloid to define and diagnose AD and that the time has come to face our fears and reject the amyloid cascade hypothesis.
authors.affiliation: 1] Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong. [2] State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Kowloon, Hong Kong.
authors.forename: Karl
authors.identifier: 0000000177865844
authors.initials: K
authors.lastname: Herrup
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D006801:Humans; D008959:Models, Neurological
chemical_list: D016229:Amyloid beta-Peptides