The pathogenesis of Alzheimer's disease: a reevaluation of the "amyloid cascade hypothesis"


The most influential theory to explain the pathogenesis of Alzheimer's disease (AD) has been the "Amyloid Cascade Hypothesis" (ACH) first formulated in 1992. The ACH proposes that the deposition of ß-amyloid (Aß) is the initial pathological event in AD leading to the formation of senile plaques (SPs) and then to neurofibrillary tangles (NFTs) death of neurons, and ultimately dementia. This paper examines two questions regarding the ACH: (1) is there a relationship between the pathogenesis of SPs and NFTs, and (2) what is the relationship of these lesions to disease pathogenesis? These questions are examined in relation to studies of the morphology and molecular determinants of SPs and NFTs, the effects of gene mutation, degeneration induced by head injury, the effects of experimentally induced brain lesions, transgenic studies, and the degeneration of anatomical pathways. It was concluded that SPs and NFTs develop independently and may be the products rather than the causes of neurodegeneration in AD. A modification to the ACH is proposed which may better explain the pathogenesis of AD, especially of late-onset cases of the disease.

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Divisions: College of Health & Life Sciences > School of Optometry > Optometry
College of Health & Life Sciences > School of Optometry > Optometry & Vision Science Research Group (OVSRG)
College of Health & Life Sciences
College of Health & Life Sciences > School of Optometry > Vision, Hearing and Language
College of Health & Life Sciences > Clinical and Systems Neuroscience
Additional Information: Copyright © 2011 R. A. Armstrong. 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.
Uncontrolled Keywords: pathogenesis,Alzheimer's disease,Amyloid Cascade Hypothesis,ACH,β-amyloid,beta-amyloid,senile plaques,neurofibrillary tangles,death of neurons,dementia,morphology determinants,molecular determinants,gene mutation,degeneration,head injury,brain lesions,transgenic studies,anatomical pathways,neurodegeneration,Clinical Neurology,Behavioral Neuroscience,Cognitive Neuroscience,Ageing,Cellular and Molecular Neuroscience,Neurology
Publication ISSN: 2090-0252
Last Modified: 10 Jun 2024 07:09
Date Deposited: 09 May 2011 13:29
Full Text Link: http://www.sage ... ad/2011/630865/
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2011
Authors: Armstrong, Richard A. (ORCID Profile 0000-0002-5046-3199)

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