Positive Feedback Loops in Alzheimer’s Disease – The Alzheimer’s Feedback HypothesisCitation formats

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Positive Feedback Loops in Alzheimer’s Disease – The Alzheimer’s Feedback Hypothesis. / Doig, Andrew.

In: Journal of Alzheimer's Disease, Vol. 66, No. 1, 2018, p. 25-36.

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Doig, Andrew. / Positive Feedback Loops in Alzheimer’s Disease – The Alzheimer’s Feedback Hypothesis. In: Journal of Alzheimer's Disease. 2018 ; Vol. 66, No. 1. pp. 25-36.

Bibtex

@article{83ebbd7ac43d4c5888bfec5ce2cae1ce,
title = "Positive Feedback Loops in Alzheimer’s Disease – The Alzheimer’s Feedback Hypothesis",
abstract = "The dominant model for Alzheimer’s Disease (AD) is the amyloid cascade hypothesis, in which the accumulation of excess amyloid- (A) leads to inflammation, excess glutamate and intracellular calcium, oxidative stress, tau hyperphosphorylation and tangle formation, neuronal loss, and ultimately dementia. In a cascade, AD proceeds in a unidirectional fashion, with events only affecting downstream processes. Compelling evidence now exists for the presence of positive feedback loops in AD, however, involving oxidative stress, inflammation, glutamate, calcium and tau. The pathological state of AD is thus a system of positive feedback loops, leading to amplification of the initial perturbation, rather than a linear cascade. Drugs may therefore be effective by targeting numerous points within the loops, rather than concentrating on upstream processes. Anti-inflammatories and anti-oxidants may be especially valuable, since these processes are involved in many loops and hence would affect numerous processes in AD.",
keywords = "systems biology, amyloid, peptide, drug discovery, directed acyclic graph, amyloid precursor protein, aggregation",
author = "Andrew Doig",
year = "2018",
doi = "10.3233/JAD-180583",
language = "English",
volume = "66",
pages = "25--36",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "1",

}

RIS

TY - JOUR

T1 - Positive Feedback Loops in Alzheimer’s Disease – The Alzheimer’s Feedback Hypothesis

AU - Doig, Andrew

PY - 2018

Y1 - 2018

N2 - The dominant model for Alzheimer’s Disease (AD) is the amyloid cascade hypothesis, in which the accumulation of excess amyloid- (A) leads to inflammation, excess glutamate and intracellular calcium, oxidative stress, tau hyperphosphorylation and tangle formation, neuronal loss, and ultimately dementia. In a cascade, AD proceeds in a unidirectional fashion, with events only affecting downstream processes. Compelling evidence now exists for the presence of positive feedback loops in AD, however, involving oxidative stress, inflammation, glutamate, calcium and tau. The pathological state of AD is thus a system of positive feedback loops, leading to amplification of the initial perturbation, rather than a linear cascade. Drugs may therefore be effective by targeting numerous points within the loops, rather than concentrating on upstream processes. Anti-inflammatories and anti-oxidants may be especially valuable, since these processes are involved in many loops and hence would affect numerous processes in AD.

AB - The dominant model for Alzheimer’s Disease (AD) is the amyloid cascade hypothesis, in which the accumulation of excess amyloid- (A) leads to inflammation, excess glutamate and intracellular calcium, oxidative stress, tau hyperphosphorylation and tangle formation, neuronal loss, and ultimately dementia. In a cascade, AD proceeds in a unidirectional fashion, with events only affecting downstream processes. Compelling evidence now exists for the presence of positive feedback loops in AD, however, involving oxidative stress, inflammation, glutamate, calcium and tau. The pathological state of AD is thus a system of positive feedback loops, leading to amplification of the initial perturbation, rather than a linear cascade. Drugs may therefore be effective by targeting numerous points within the loops, rather than concentrating on upstream processes. Anti-inflammatories and anti-oxidants may be especially valuable, since these processes are involved in many loops and hence would affect numerous processes in AD.

KW - systems biology

KW - amyloid

KW - peptide

KW - drug discovery

KW - directed acyclic graph

KW - amyloid precursor protein

KW - aggregation

U2 - 10.3233/JAD-180583

DO - 10.3233/JAD-180583

M3 - Article

VL - 66

SP - 25

EP - 36

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 1

ER -