Cited by 84Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsAdvanced Glycation End Products research

Amyloid β: one of three danger‐associated molecules that are secondary inducers of the proinflammatory cytokines that mediate A lzheimer's disease

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Clark, I A, Vissel, B·2015·British Journal of Pharmacology

Abstract

This review concerns how the primary inflammation preceding the generation of certain key damage-associated molecular patterns (DAMPs) arises in Alzheimer's disease (AD). In doing so, it places soluble amyloid β (Aβ), a protein hitherto considered as a primary initiator of AD, in a novel perspective. We note here that increased soluble Aβ is one of the proinflammatory cytokine-induced DAMPs recognized by at least one of the toll-like receptors on and in various cell types. Moreover, Aβ is best regarded as belonging to a class of DAMPs, as do the S100 proteins and HMBG1, that further exacerbate production of these same proinflammatory cytokines, which are already enhanced, and induces them further. Moreover, variation in levels of other DAMPs of this same class in AD may explain why normal elderly patients can exhibit high Aβ plaque levels, and why removing Aβ or its plaque does not retard disease progression. It may also explain why mouse transgenic models, having been designed to generate high Aβ, can be treated successfully by this approach.

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Authors
Clark, I. A., & Vissel, B.
Affiliations
  • Australian National University (AU)
  • Garvan Institute of Medical Research (AU)
Corresponding author
Clark, I A
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2015-06-29
Volume
172
Issue
15
Pages
3714-3727
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
OpenAlex
W1590561022
Cited by
84
References
217
Citations by year
2026: 4 · 2025: 7 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 11 · 2020: 6 · 2019: 6 · 2018: 16 · 2017: 10 · 2016: 8 · 2015: 1
FWCI
1.43
Type
journal article
Language
en
Open access
Locations
  • British Journal of Pharmacology (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • ANU Open Research (Australian National University) (submittedVersion)
  • UTS ePRESS (University of Technology Sydney) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Keywords
amyloid-beta, Alzheimer's disease, damage-associated molecular patterns, inflammatory cytokines, Toll-like receptors, S-100 protein, neuroinflammation, amyloid plaques, transgenic mouse model, disease progression
MeSH terms
Pathogen-Associated Molecular Pattern Molecules, Alzheimer Disease, Animals, Humans, Cytokines, Amyloid beta-Peptides, Inflammation Mediators, Lactic Acid

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