Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain
Abstract
We assessed whether the intracellular bacterium Chlamydia pneumoniae was present in post-mortem brain samples from patients with and without late-onset Alzheimer's disease (AD), since some indirect evidence seems to suggest that infection with the organism might be associated with the disease. Nucleic acids prepared from those samples were screened by polymerase chain reaction (PCR) assay for DNA sequences from the bacterium, and such analyses showed that brain areas with typical AD-related neuropathology were positive for the organism in 17/19 AD patients. Similar analyses of identical brain areas of 18/19 control patients were PCR-negative. Electron- and immunoelectron-microscopic studies of tissues from affected AD brain regions identified chlamydial elementary and reticulate bodies, but similar examinations of non-AD brains were negative for the bacterium. Culture studies of a subset of affected AD brain tissues for C. pneumoniae were strongly positive, while identically performed analyses of non-AD brain tissues were negative. Reverse transcription (RT)-PCR assays using RNA from affected areas of AD brains confirmed that transcripts from two important C. pneumoniae genes were present in those samples but not in controls. Immunohistochemical examination of AD brains, but not those of controls, identified C. pneumoniae within pericytes, microglia, and astroglia. Further immunolabelling studies confirmed the organisms' intracellular presence primarily in areas of neuropatho…
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?
90% of post-mortem patient brains from late-onset dementia patients contained C. pneumoniae DNA, compared with only 5% of control age-matched brains.
“In the late 1990s, it was shown that 90% of such post-mortem patient brains contained C. pneumoniae DNA, compared with only 5% of control age-matched brains9,10.”
From Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer’s disease risk (2022) · cites this paper as [9]
C. pneumoniae antigens have been detected inside both astrocytes and microglia in post-mortem human brains.
“C. pneumoniae antigens have been detected inside both astrocytes and microglia in post-mortem human brains9,11,67,68.”
From Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer’s disease risk (2022) · cites this paper as [9]
Microglia and astrocytes act as host cells of C. pneumoniae in Alzheimer's disease brain.
“Previous studies have shown that microglia and astrocytes act as host cells of C. pneumoniae in Alzheimer’s disease brain9.”
From Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer’s disease risk (2022) · cites this paper as [9]
Cites
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · see citing works
A68: a Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau
Lee, V. M.-Y., Balin, B. J., Otvos, L., & Trojanowski, J. Q. (1991) · Science · doi:10.1126/science.1899488 · Cited by 1,418 · cited 1× · see citing works
“tau is a normal component of the neuronal cytoskeleton, and evidence suggests that its abnormal deposition in NFTs, NTs, and dystrophic neurites results from various types of aberrant post-translational modification of the protein [1, 2, 49, 91].”
BackgroundSelf-citationStyren, S. D., Civin, W. H., & Rogers, J. (1990) · Experimental Neurology · doi:10.1016/0014-4886(90)90054-v · Cited by 191 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
Gavazzi, G., & Krause, K.-H. (2002) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(02)00437-1 · Cited by 990 · see citing works
Thorne, R. G., Pronk, G. J., Padmanabhan, V., & Frey, W. H. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.029 · Cited by 958 · see citing works
Ilievski, V., Zuchowska, P. K., Green, S. J., Toth, P. T., Ragozzino, M. E., Le, K., Aljewari, H. W., O’Brien-Simpson, N. M., Reynolds, E. C., & Watanabe, K. (2018) · PLOS ONE · doi:10.1371/journal.pone.0204941 · Cited by 372 · see citing works
Alzheimer’s disease and gut microbiota
Hu, X., Wang, T., & Jin, F. (2016) · Science China Life Sciences · doi:10.1007/s11427-016-5083-9 · Cited by 371 · see citing works
The Physiological Roles of Amyloid-β Peptide Hint at New Ways to Treat Alzheimer's Disease
Brothers, H. M., Gosztyla, M. L., & Robinson, S. R. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00118 · Cited by 314 · see citing works
Harris, S. A., & Harris, E. A. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-142853 · Cited by 279 · see citing works
Kumar, P. S. (2017) · The Journal of Physiology · doi:10.1113/jp272427 · Cited by 241 · see citing works
Inflammation Induced by Infection Potentiates Tau Pathological Features in Transgenic Mice
Sy, M., Kitazawa, M., Medeiros, R., Whitman, L., Cheng, D., Lane, T. E., & LaFerla, F. M. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.02.012 · Cited by 210 · see citing works
Bacterial Infection and Alzheimer's Disease: A Meta-Analysis
Maheshwari, P., & Eslick, G. D. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-140621 · Cited by 183 · see citing works
Can a Bacterial Endotoxin be a Key Factor in the Kinetics of Amyloid Fibril Formation?
Asti, A., & Gioglio, L. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-131394 · Cited by 180 · see citing works
The Possibility of an Infectious Etiology of Alzheimer Disease
Ashraf, G. M., Tarasov, V. V., Makhmutovа, A., Chubarev, V. N., Avila-Rodriguez, M., Bachurin, S. O., & Aliev, G. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1388-y · Cited by 175 · see citing works
Time to test antibacterial therapy in Alzheimer’s disease
Panza, F., Lozupone, M., Solfrizzi, V., Watling, M., & Imbimbo, B. P. (2019) · Brain · doi:10.1093/brain/awz244 · Cited by 161 · see citing works
Immunohistological detection of Chlamydia pneumoniae in the Alzheimer's disease brain
Hammond, C. J., Hallock, L. R., Howanski, R. J., Appelt, D. M., Little, C. S., & Balin, B. J. (2010) · BMC Neuroscience · doi:10.1186/1471-2202-11-121 · Cited by 156 · see citing works
Self-citationInfectious burden and cognitive function: The Northern Manhattan Study
Katan, M., Moon, Y. P., Paik, M. C., Sacco, R. L., Wright, C. B., & Elkind, M. S. V. (2013) · Neurology · doi:10.1212/wnl.0b013e3182896e79 · Cited by 141 · see citing works
Infectious agents and Alzheimer's disease
Piekut, T., Hurła, M., Banaszek, N., Szejn, P., Dorszewska, J., Kozubski, W., & Prendecki, M. (2022) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2102073 · Cited by 123 · see citing works
Patrick, K. L., Bell, S. L., Weindel, C. G., & Watson, R. O. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00138 · Cited by 110 · see citing works
Polymicrobial Infections In Brain Tissue From Alzheimer’s Disease Patients
Pisa, D., Alonso, R., Fernández-Fernández, A. M., Rábano, A., & Carrasco, L. (2017) · Scientific Reports · doi:10.1038/s41598-017-05903-y · Cited by 114 · see citing works
Baune, B. T., Rothermundt, M., Ladwig, K. H., Meisinger, C., & Berger, K. (2011) · AGE · doi:10.1007/s11357-010-9165-5 · Cited by 95 · see citing works
Physiological Roles of Amyloid-?? and Implications for its Removal in Alzheimer???s Disease
Bishop, G. M., & Robinson, S. R. (2004) · Drugs & Aging · doi:10.2165/00002512-200421100-00001 · Cited by 94 · see citing works
Vojtechova, I., Machacek, T., Kristofikova, Z., Stuchlik, A., & Petrasek, T. (2022) · PLOS Pathogens · doi:10.1371/journal.ppat.1010929 · Cited by 92 · see citing works
Chacko, A., Delbaz, A., Walkden, H., Basu, S., Armitage, C. W., Eindorf, T., Trim, L. K., Miller, E., West, N. P., St John, J. A., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-06749-9 · Cited by 65 · see citing works
Do infectious agents play a role in dementia?
Dobson, C. B., Wozniak, M. A., & Itzhaki, R. F. (2003) · Trends in Microbiology · doi:10.1016/s0966-842x(03)00146-x · Cited by 56 · see citing works
Infectious burden and cognitive decline in the northern Manhattan study
Wright, C. B., Gardener, H., Dong, C., Yoshita, M., DeCarli, C., Sacco, R. L., Stern, Y., & Elkind, M. S. V. (2015) · Journal of the American Geriatrics Society · doi:10.1111/jgs.13557 · Cited by 52 · see citing works
When the infectious environment meets the AD brain
Ganz, T., Fainstein, N., & Ben-Hur, T. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00559-3 · Cited by 39 · see citing works
Herpes viruses and Alzheimer's disease: new evidence in the debate
Balin, B. J., & Hudson, A. P. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30316-8 · Cited by 38 · see citing works
Self-citationThe Role of Genetic, Environmental, and Dietary Factors in Alzheimer’s Disease: A Narrative Review
Mertaş, B., & Boşgelmez, İ. İ. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26031222 · Cited by 35 · see citing works
Andreadou, E. G., Katsipis, G., Tsolaki, M., & Pantazaki, A. A. (2021) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2021.577561 · Cited by 31 · see citing works
A reappraisal on amyloid cascade hypothesis: The role of chronic infection in Alzheimer’s disease
Phuna, Z. X., & Madhavan, P. (2023) · International Journal of Neuroscience · doi:10.1080/00207454.2022.2045290 · Cited by 12 · see citing works
- Authors
- Balin, B. J., Gérard, H. C., Arking, E. J., Appelt, D. M., Branigan, P. J., Abrams, J. T., Whittum-Hudson, J. A., & Hudson, A. P.
- Affiliations
- United States Department of Veterans Affairs (US)
- Venue
- Medical Microbiology and Immunology
- Published
- 1998-08-10
- Volume
- 187
- Issue
- 1
- Pages
- 23-42
- ISSN
- 0044-3077 (ISSN-L)
- 0300-8584
- 1432-1831
- OpenAlex
- W2069453256
- Cited by
- 506
- References
- 3
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 22 · 2023: 19 · 2022: 24 · 2021: 28 · 2020: 28 · 2019: 23 · 2018: 22 · 2017: 8 · 2016: 19 · 2015: 14 · 2014: 20 · 2013: 11 · 2012: 12
- FWCI
- 9.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Medical Microbiology and Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG10160, R29AG010160)
- National Eye Institute (EY03324, R01EY003324)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR42541, R01AR042541)
- 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
- Chlamydia pneumoniae, Alzheimer's disease, late-onset Alzheimer's disease, intracellular bacteria, neuropathology, pericytes, microglia, astrocytes, elementary bodies, reticulate bodies, bacterial gene expression, postmortem brain
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Antibodies, Monoclonal, Brain, DNA, Bacterial, Female, Genes, Bacterial, Humans, Immunohistochemistry, Male, Microscopy, Electron, Middle Aged, RNA, Bacterial, Polymerase Chain Reaction, Chlamydophila pneumoniae
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
