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

Richard A. Armstrong

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Article number630865
JournalInternational Journal of Alzheimer's Disease
Volume2011
DOIs
Publication statusPublished - 2011

Fingerprint

Neurofibrillary Tangles
Amyloid
Amyloid Plaques
Alzheimer Disease
Craniocerebral Trauma
Dementia
Neurons
Mutation
Brain
Genes

Bibliographical note

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.

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

Cite this

@article{5d5335fb4dc544ac87fa8c2910cc4d43,
title = "The pathogenesis of Alzheimer's disease: a reevaluation of the {"}amyloid cascade hypothesis{"}",
abstract = "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 (A{\ss}) 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.",
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",
author = "Armstrong, {Richard A.}",
note = "Copyright {\circledC} 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.",
year = "2011",
doi = "10.4061/2011/630865",
language = "English",
volume = "2011",
journal = "International Journal of Alzheimer's Disease",
issn = "2090-8024",
publisher = "Hindawi Publishing Corporation",

}

The pathogenesis of Alzheimer's disease: a reevaluation of the "amyloid cascade hypothesis". / Armstrong, Richard A.

In: International Journal of Alzheimer's Disease, Vol. 2011, 630865, 2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The pathogenesis of Alzheimer's disease: a reevaluation of the "amyloid cascade hypothesis"

AU - Armstrong, Richard A.

N1 - 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.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - pathogenesis

KW - Alzheimer's disease

KW - Amyloid Cascade Hypothesis

KW - ACH

KW - β-amyloid

KW - beta-amyloid

KW - senile plaques

KW - neurofibrillary tangles

KW - death of neurons

KW - dementia

KW - morphology determinants

KW - molecular determinants

KW - gene mutation

KW - degeneration

KW - head injury

KW - brain lesions

KW - transgenic studies

KW - anatomical pathways

KW - neurodegeneration

UR - http://www.scopus.com/inward/record.url?scp=79953276681&partnerID=8YFLogxK

U2 - 10.4061/2011/630865

DO - 10.4061/2011/630865

M3 - Article

VL - 2011

JO - International Journal of Alzheimer's Disease

JF - International Journal of Alzheimer's Disease

SN - 2090-8024

M1 - 630865

ER -