Lower Counts of Astroglia and Activated Microglia in Patients with Alzheimer's Disease with Regular Use of Non-Steroidal Anti-Inflammatory Drugs
Abstract
Epidemiological studies have indicated that non-steroidal anti-inflammatory drugs (NSAID) may have some therapeutic effect in Alzheimer's disease (AD) and experimental studies have shown that microglia activation by Abeta-peptide (Abeta-peptide. Furthermore, our results indicate that regular NSAID use is associated with significantly lower counts of astrocytes and a trend of lower counts of activated microglia in the brain tissue. The influence of NSAID use was noted in all ApoE genotypes however the trend of lower counts of glial cells with regular NSAID use was more marked in patients carrying the ApoE varepsilon 4/4 alleles. Based on our results one would anticipate that regular NSAID dosing could have a beneficial effect on the progression of the disease. However, the fact that we failed to observe significant differences for activated microglia might indicate an age or stage dependent difference in the glial response i.e. in their activation rate. More studies into age and stage related factors influencing the glial response are required if one is to devise novel pharmacological treatment strategies for AD.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NSAIDs might protect against AD by targeting underlying neuroinflammation.
“NSAIDs might protect against AD by targeting underlying neuroinflammation.95”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [95]
Cites
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · see citing works
Activation of microglial cells by β-amyloid protein and interferon-γ
Meda, L., Cassatella, M. A., Szendrei, G. I., Otvos, L., Baron, P., Villalba, M., Ferrari, D., & Rossi, F. (1995) · Nature · doi:10.1038/374647a0 · Cited by 1,314 · see citing works
Microglia: Intrinsic immuneffector cell of the brain
Gehrmann, J., Matsumoto, Y., & Kreutzberg, G. W. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(94)00015-h · Cited by 1,111 · see citing works
Clinical trial of indomethacin in Alzheimer's disease
Rogers, J., Kirby, L., Hempelman, S. R., Berry, D. A., McGeer, P. L., Kaszniak, A. W., Zalinski, J., Cofield, M., Mansukhani, L., Willson, P., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1609 · Cited by 991 · see citing works
Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E
Barger, S. W., & Harmon, A. D. (1997) · Nature · doi:10.1038/42257 · Cited by 622 · see citing works
Diedrich, J. F., Minnigan, H. J., Carp, R. I., Whitaker, J. N., Race, R., Frey, W. H., & Haase, A. T. (1991) · Journal of Virology · doi:10.1128/jvi.65.9.4759-4768.1991 · Cited by 295 · see citing works
THE ROLE OF ANTI-INFLAMMATORY DRUGS IN THE PREVENTION AND TREATMENT OF ALZHEIMER'S DISEASE
Breitner, J. C. S. (1996) · Annual Review of Medicine · doi:10.1146/annurev.med.47.1.401 · Cited by 263 · see citing works
Nagy, Z. S., Esiri, M. M., Jobst, K. A., Johnston, C., Litchfield, S., Sim, E., & Smith, A. D. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00331-c · Cited by 250 · see citing works
(1990) · PubMed Central · Cited by 214 · see citing works
Microglial Activation in Alzheimer Disease: Association with APOE Genotype
Egensperger, R., Kösel, S., von Eitzen, U., & Graeber, M. B. (1998) · Brain Pathology · doi:10.1111/j.1750-3639.1998.tb00166.x · Cited by 164 · see citing works
DIPATRE, P. L., & GELMAN, B. B. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199702000-00004 · Cited by 157 · see citing works
Arnold, S. E., Franz, B. R., Trojanowski, J. Q., Moberg, P. J., & Gur, R. E. (1996) · Acta Neuropathologica · doi:10.1007/s004010050425 · Cited by 112 · see citing works
Morphometric Analysis of Microglia in Alzheimerʼs Disease
CARPENTER, A. F., CARPENTER, P. W., & MARKESBERY, W. R. (1993) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199311000-00007 · Cited by 94 · see citing works
Indomethacin Reverses the Microglial Response to Amyloid β-Protein
Netland, E. E., Newton, J. L., Majocha, R. E., & Tate, B. A. (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00047-5 · Cited by 93 · see citing works
Apolipoprotein E, memory and Alzheimer's disease
Soininen, H. S., & Riekkinen, P. J. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10027-8 · Cited by 91 · see citing works
Self-citationOvermyer, M., Helisalmi, S., Soininen, H., Laakso, M., Riekkinen Sr., P., & Alafuzoff, I. (1999) · Acta Neuropathologica · doi:10.1007/s004010051002 · Cited by 91 · see citing works
Self-citationAstrogliosis and the ApoE Genotype
Overmyer, M., Helisalmi, S., Soininen, H. S., Laakso, M., Riekkinen, P., & Alafuzoff, I. I. (1999) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017128 · Cited by 68 · see citing works
Self-citationAlzheimer's disease: neuropathological correlates of cognitive and motor disorders
Mölsä, P. K., Säkö, E., Paljärvi, L., Rinne, J. O., & Rinne, U. K. (1987) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1987.tb05465.x · Cited by 68 · see citing works
Irina, A., Seppo, H., Arto, M., Paavo, R., & Hilkka, S. (1999) · Stroke · doi:10.1161/01.str.30.3.613 · Cited by 58 · see citing works
Expression of apolipoprotein E by mouse brain astrocytes and its modulation by interferon-γ
Oropeza, R. L., Wekerle, H., & Werb, Z. (1987) · Brain Research · doi:10.1016/s0006-8993(87)80018-5 · Cited by 42 · see citing works
Glial Cells in Alzheimer's Disease: Preferential Effect of APOE Risk on Scattered Microglia
Saitoh, T., Kang, D. E., Mallory, M. E., Teresa, R. D., & Masliah, E. (2009) · Gerontology · doi:10.1159/000213839 · Cited by 23 · see citing works
Pitfalls in the quantitative estimation of β-amyloid immunoreactivity in human brain tissue
Kraszpulski, M., Soininen, H. S., Riekkinen, P. J., & Alafuzoff, I. I. (1998) · Histochemistry and Cell Biology · doi:10.1007/s004180050305 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Neuroinflammatory processes in Alzheimer’s disease
Heneka, M. T., O’Banion, M. K., Terwel, D., & Kummer, M. P. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0438-z · Cited by 433 · see citing works
Contribution of inflammatory processes to Alzheimer's disease: molecular mechanisms
Sastre, M., Klockgether, T., & Heneka, M. T. (2006) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2005.11.014 · Cited by 426 · see citing works
Garwood, C. J., Ratcliffe, L. E., Simpson, J. E., Heath, P. R., Ince, P. G., & Wharton, S. B. (2017) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12338 · Cited by 233 · see citing works
Albertini, C., Salerno, A., de Sena Murteira Pinheiro, P., & Bolognesi, M. L. (2021) · Medicinal Research Reviews · doi:10.1002/med.21699 · Cited by 179 · see citing works
Tracking neuroinflammation in Alzheimer’s disease: the role of positron emission tomography imaging
Zimmer, E. R., Leuzy, A., Benedet, A. L., Breitner, J., Gauthier, S., & Rosa-Neto, P. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-120 · Cited by 121 · see citing works
Molecular targets of non-steroidal anti-inflammatory drugs in neurodegenerative diseases
Lleo, A., Galea, E., & Sastre, M. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-6516-1 · Cited by 93 · see citing works
Pharmacokinetics of Cromolyn and Ibuprofen in Healthy Elderly Volunteers
Brazier, D., Perry, R., Keane, J., Barrett, K., & Elmaleh, D. R. (2017) · Clinical Drug Investigation · doi:10.1007/s40261-017-0549-5 · Cited by 31 · see citing works
- Authors
- Alafuzoff, I., Overmyer, M., Helisalmi, S., & Soininen, H.
- Affiliations
- Kuopio University Hospital (FI)
- Department of Neuroscience and Neurology, Kuopio University, Kuopio, Finland
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2000-04-01
- Volume
- 2
- Issue
- 1
- Pages
- 37-46
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1672086017
- Cited by
- 42
- References
- 23
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- 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, nonsteroidal anti-inflammatory drugs
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review