Cited by 975Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Inflammation in Alzheimer Disease--A Brief Review of the Basic Science and Clinical Literature

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Wyss-Coray, T., Rogers, J.·2012·Cold Spring Harbor Perspectives in Medicine

Abstract

Biochemical and neuropathological studies of brains from individuals with Alzheimer disease (AD) provide clear evidence for an activation of inflammatory pathways, and long-term use of anti-inflammatory drugs is linked with reduced risk to develop the disease. As cause and effect relationships between inflammation and AD are being worked out, there is a realization that some components of this complex molecular and cellular machinery are most likely promoting pathological processes leading to AD, whereas other components serve to do the opposite. The challenge will be to find ways of fine tuning inflammation to delay, prevent, or treat AD.

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Crossref · 10.1101/cshperspect.a006346

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252 of 252 references verified0 citation errors · 0 not checkable

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  • Microglia and complement activation are prominently involved in plaque maintenance and related peri-plaque neuropathology.

    “Although microglia and complement activation are prominently involved in plaque maintenance and related peri-plaque neuropathology, their roles have heretofore been largely regarded as a secondary event related to neuroinflammation (2).”

    From Complement and microglia mediate early synapse loss in Alzheimer mouse models (2016) · cites this paper as [2]

    The CELLULAR MEDIATORS Microglia section describes microglia gathering around plaques and interacting with amyloid deposits; the MOLECULAR MEDIATORS section reports complement at plaques and evidence that C3 may help microglia clear amyloid. But the review says it remains unclear whether microglia directly cause the neuronal damage observed near plaques. It does not establish the claimed role in peri-plaque neuropathology as firmly as the citing sentence suggests. (LLM, conf=0.83)

    Experimental — accuracy not yet measured
  • Sustained inflammation contributes to neurodegeneration.

    “but sustained inflammation contributes to neurodegeneration12”

    From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [12]

    The Conclusions (page not provided) say increased peripheral inflammation leads to more neurodegeneration in animal models and possibly in Alzheimer disease. That supports a contribution from inflammation, but the review also describes inflammatory responses as potentially protective; it does not establish that sustained inflammation generally causes neurodegeneration. (LLM, conf=0.82)

    Experimental — accuracy not yet measured
  • Numerous cytokines and chemokines are expressed at abnormal levels in AD.

    “Numerous cytokines and chemokines are expressed at abnormal levels in AD [76].”
  • In the AD brain, reactive microglia cluster around Aβ plaques.

    “In the AD brain, reactive microglia cluster around Aβ plaques12”
  • A SASP factor specific to senescent microglia has not been identified, and several components of the SASP can be attributed to the secreted inflammatory milieu of non-senescent 'activated' microglia.

    “However, a SASP factor specific to senescent microglia has not been identified, and several components of the SASP can be attributed to the secreted inflammatory milieu of non-senescent ‘activated’ microglia [93].”

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Research works printed but not linked: 1

  1. [92]92. Holers VM. 1996. Complement. In Clinical immunology principles and practice (ed. Rich RR), pp. 363-391.

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Authors
Wyss-Coray, T., & Rogers, J.
Affiliations
VA Palo Alto Health Care System (US)
Corresponding author
Rogers, J.
Venue
Cold Spring Harbor Perspectives in Medicine
Published
2011-11-15
Volume
2
Issue
1
Pages
a006346-a006346
ISSN
2157-1422 (ISSN-L)
OpenAlex
W2107376426
Cited by
975
References
252
Citations by year
2026: 22 · 2025: 32 · 2024: 51 · 2023: 62 · 2022: 48 · 2021: 98 · 2020: 89 · 2019: 89 · 2018: 94 · 2017: 89 · 2016: 76 · 2015: 84 · 2014: 67 · 2013: 52 · 2012: 21
Type
posted content
Language
en
Open access
Locations
  • Cold Spring Harbor Perspectives in Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • National Institutes of Health
  • National Institute on Aging (R01AG027505, AG 07367, AG27505)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, neuroinflammation, anti-inflammatory agents, neurodegeneration, neuroprotection
MeSH terms
Alzheimer Disease, Animals, Anti-Inflammatory Agents, Astrocytes, Clinical Trials as Topic, Complement System Proteins, Complement Activation, Encephalitis, Humans, Neurons, Oligodendroglia, Polymorphism, Genetic, Prostaglandin-Endoperoxide Synthases, Cytokines, Arachidonic Acid, Microglia, Toll-Like Receptors, Mice

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