Inflammation in Alzheimer Disease--A Brief Review of the Basic Science and Clinical Literature
Open accessAbstract
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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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 measuredSustained 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 measuredNumerous 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”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [12]
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].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [93]
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TNFRSF1B Gene Variants and Related Soluble TNFR2 Levels Impact Resilience in Alzheimer’s Disease
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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
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-11-15
- Volume
- 2
- Issue
- 1
- Pages
- a006346-a006346
- ISSN
- 2157-1422 (ISSN-L)
- PMC
- PMC3253025
- 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
- bronze
- doi.org
- 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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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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