NSAIDs and Alzheimer disease: Epidemiological, animal model and clinical studies
Abstract
This review reports correlations between four independent fields related to inflammation and Alzheimer disease: fundamental pathology, epidemiology, transgenic animal studies and clinical trials. Activated microglia, along with a spectrum of inflammatory mediators, have been identified in association with the lesions of Alzheimer disease (AD), suggesting that antiinflammatory agents such as NSAIDs should protect against the disease. In multiple epidemiological investigations testing this hypothesis, a significant risk reduction, or a trend towards such a reduction has been observed in long term as opposed to short term users of traditional NSAIDs. In studies where such NSAIDs have been administered to AD transgenic mice, a dose dependent reduction in pathology was observed. The selective C0X-2 inhibitors were ineffective. Results of clinical investigations have so far been disappointing but have nevertheless correlated with fundamental pathological findings and with transgenic mouse results. Four clinical trials using selective COX-2 inhibitors failed which is in keeping with the animal results and is consistent with pathological findings demonstrating that COX-1 and not COX-2 is the appropriate target in activated human microglia. A low dose trial of the traditional NSAID naproxen also failed, but pilot trials using therapeutically established doses of indomethacin and diclofenac/misoprostol showed promise. Further clinical investigations with relatively high doses of tradit…
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The clinical translation of broad anti-inflammatory approaches has been disappointing, partly because inflammation in Alzheimer's disease is not a single harmful process that can simply be turned off.
“However, the clinical translation of broad anti-inflammatory approaches has been disappointing, partly because inflammation in Alzheimer’s disease is not a single harmful process that can simply be turned off [48,49].”
From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [48]
CD28 and B7-family pathways are deeply involved in peripheral immune regulation, so systemic manipulation could affect T-cell responses, autoimmunity, infection risk, or immunosurveillance.
“CD28 and B7-family pathways are deeply involved in peripheral immune regulation, so systemic manipulation could affect T-cell responses, autoimmunity, infection risk, or immunosurveillance.”
From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [48]
In peripheral immunology, CD28 is a central T-cell co-stimulatory receptor, and interventions affecting CD28 or its B7-family ligand network can have major consequences for immune activation, tolerance, autoimmunity, and infection risk.
“In peripheral immunology, CD28 is a central T-cell co-stimulatory receptor, and interventions affecting CD28 or its B7-family ligand network can have major consequences for immune activation, tolerance, autoimmunity, and infection risk.”
From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [48]
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Self-citationLymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis?
Chmiel, J., Gawełczyk, W., Soczyńska, J., & Leszek, J. (2026) · Cells · doi:10.3390/cells15131151
“However, the clinical translation of broad anti-inflammatory approaches has been disappointing, partly because inflammation in Alzheimer’s disease is not a single harmful process that can simply be turned off [48,49].”
- Authors
- McGeer, P. L., & McGeer, E. G.
- Affiliations
- University of British Columbia (CA)
- Corresponding author
- McGeer, Patrick L.
- ORCID
- McGeer, Patrick L.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 28
- Issue
- 5
- Pages
- 639-647
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W1991794361
- Cited by
- 498
- References
- 7
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 14 · 2023: 15 · 2022: 11 · 2021: 23 · 2020: 30 · 2019: 12 · 2018: 10 · 2017: 26 · 2016: 28 · 2015: 35 · 2014: 22 · 2013: 30 · 2012: 37
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- Alzheimer's disease, nonsteroidal anti-inflammatory drugs, neuroinflammation, microglial activation, cyclooxygenase-1, COX-2 inhibitors, indomethacin, naproxen, transgenic mouse model, anti-inflammatory therapy, clinical trials
- MeSH terms
- Alzheimer Disease, Animals, Anti-Inflammatory Agents, Non-Steroidal, Disease Models, Animal, Humans
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