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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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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Activated microglia can respond to injured neurons in a neuroprotective manner and afterwards become toxic, contributing to neuroinflammation and neurodegeneration.
“Further, activated microglia can respond to injured neurons in a neuroprotective manner and, afterwards, become toxic, contributing to neuroinflammation and neurodegeneration [15].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [15]
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Do Epigenetic Pathways Initiate Late Onset Alzheimer Disease (LOAD): Towards a New Paradigm
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Malaria Induced Endotoxin Tolerance
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Clark, I. A. (1979) · Infection and Immunity · doi:10.1128/iai.24.2.319-325.1979 · Cited by 46 · see citing works
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Systemic Release of High Mobility Group Box 1 Protein during Severe Murine Influenza
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The Sleep-Immune Crosstalk in Health and Disease
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“They do not appear to involve the classical inducers of the typical inflammatory response [i.e., infection or tissue injury (377)], but rather cellular stress or malfunction that leads to activation of PRRs by the release of DAMPs (e.g., HSPs) (68, 100).”
BackgroundInfluentialCattaneo, A., Cattane, N., Galluzzi, S., Provasi, S., Lopizzo, N., Festari, C., Ferrari, C., Guerra, U. P., Paghera, B., Muscio, C., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.08.019 · Cited by 1,382 · see citing works
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Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation
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Morris, G. P., Clark, I. A., & Vissel, B. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1918-8 · Cited by 212 · see citing works
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The Role of the Microbiota-Gut-Brain Axis in the Development of Alzheimer’s Disease
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Potential importance of B cells in aging and aging-associated neurodegenerative diseases
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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
- ORCID
- 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
- PMC
- PMC4523330
- 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
- hybrid
- doi.org
- Licence
- 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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