Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice
Abstract
Amyloid deposits resembling plaques found in Alzheimer's disease (AD) brains were formed in the brains of non-transgenic BALB/c mice following intranasal infection with Chlamydia pneumoniae. The mice were infected at 3 months of age with C. pneumoniae isolated from an AD brain. Infection was confirmed by light and electron microscopy in olfactory tissues of the mice. C. pneumoniae was still evident in these tissues 3 months after the initial infection indicating that a persistent infection had been established. Amyloid beta (Abeta) 1-42 immunoreactive deposits were identified in the brains of infected BALB/c mice up to 3 months post-infection with the density, size, and number of deposits increasing as the infection progressed. A subset of deposits exhibited thioflavin-s labeling. Intracellular Abeta1-42 labeling was observed in neuronal cells. Experimental induction of amyloid deposition in brains of non-transgenic BALB/c mice following infection with C. pneumoniae may be a useful model for furthering our understanding of mechanisms, linked to infection, involved in the initiation of the pathogenesis of sporadic AD.
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After intranasal inoculation in mice, C. pneumoniae antigens and/or infectious organisms have been detected in the olfactory mucosa and the olfactory bulb 1-4 months post intranasal inoculation.
“After intranasal inoculation in mice, C. pneumoniae antigens and/or infectious organisms have been detected in the olfactory mucosa and the olfactory bulb 1–4 months post intranasal inoculation16–18, and C. pneumoniae DNA in these tissues has been detected 1 week after inoculation18, strongly suggesting that the bacteria can infect the CNS via the olfactory nerve.”
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 [16]
C. pneumoniae DNA, antigen and/or live bacteria have been detected in the brain of inoculated mice, which resulted in Aβ deposition or altered appearance of Aβ deposits.
“C. pneumoniae DNA, antigen and/or live bacteria have been detected in the brain of inoculated mice15–18, which resulted in Aβ deposition16,17 or altered appearance of Aβ deposits18.”
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 [16]
The mice used in these studies were wild-type mice and not mouse models of Alzheimer's disease, suggesting that C. pneumoniae can contribute to the neuropathologies associated with late-onset dementia.
“Importantly, the mice used in these studies were wild-type mice and not mouse models of Alzheimer’s disease, suggesting that C. pneumoniae can contribute to the neuropathologies associated with late-onset dementia.”
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 [16]
Previous studies have shown that Aβ accumulation after C. pneumoniae inoculation occurs after months.
“Whilst previous studies have shown that this occurs after months16–18, if the bacteria reach the CNS more rapidly, alterations in Aβ deposition may also occur sooner.”
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 [16]
Control uninfected mice exhibited diffuse Aβ deposits.
“while control uninfected mice exhibited diffuse Aβ deposits (Fig. 5P) which is similar to previous reports16,18,50.”
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 [16]
The faster time-frame may be due to differences in inoculation dose since they used a higher dose than two previous studies but lower than another.
“which may be due to differences in the inoculation dose since we used a higher inoculation dose than two previous studies16,50 but lower than another18.”
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 [16]
The time-frame for infection of the CNS by C. pneumoniae was considerably faster than what has previously been shown (1 week-3 months).
“The time-frame for infection of the CNS by C. pneumoniae was considerably faster than what has previously been shown (1 week–3 months16–18)”
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 [16]
Cites
Time Course of the Development of Alzheimer-like Pathology in the Doubly Transgenic PS1+APP Mouse
Gordon, M. N., Holcomb, L. A., Jantzen, P. T., DiCarlo, G., Wilcock, D., Boyett, K. W., Connor, K., Melachrino, J., O'Callaghan, J. P., & Morgan, D. (2002) · Experimental Neurology · doi:10.1006/exnr.2001.7754 · Cited by 247 · see citing works
Lue, L.-F., Brachova, L., Civin, H. W., & Rogers, J. (1996) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199655100-00008 · Cited by 246 · cited 2× · see citing works
“Although inflammation in AD, as a result of A deposition, is accepted as a major mechanism in overall pathogenesis [24], C.”
BackgroundWirths, O., Multhaup, G., Czech, C., Feldmann, N., Blanchard, V., Tremp, G., Beyreuther, K., Pradier, L., & Bayer, T. A. (2002) · Brain Pathology · doi:10.1111/j.1750-3639.2002.tb00442.x · Cited by 125 · see citing works
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Kumar, D. K. V., Choi, S. H., Washicosky, K. J., Eimer, W. A., Tucker, S., Ghofrani, J., Lefkowitz, A., McColl, G., Goldstein, L. E., Tanzi, R. E., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf1059 · Cited by 971 · 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
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
Mechanisms of Molecular Mimicry Involving the Microbiota in Neurodegeneration
Friedland, R. P. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-142841 · Cited by 338 · 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
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
Luca, M., Di Mauro, M., Di Mauro, M., & Luca, A. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/4730539 · Cited by 190 · 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
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 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
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
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
Clark, I. A., & Vissel, B. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13181 · Cited by 84 · 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
The 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
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
- Little, C. S., Hammond, C. J., MacIntyre, A., Balin, B. J., & Appelt, D. M.
- Affiliations
- Philadelphia College of Osteopathic Medicine (US)
- Corresponding author
- Appelt, Denah M
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 25
- Issue
- 4
- Pages
- 419-429
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2113944963
- Cited by
- 243
- References
- 3
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 11 · 2023: 11 · 2022: 15 · 2021: 16 · 2020: 12 · 2019: 8 · 2018: 11 · 2017: 7 · 2016: 15 · 2015: 9 · 2014: 14 · 2013: 12 · 2012: 6
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons - PCOM (Philadelphia College of Osteopathic Medicine) (submittedVersion)
- 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, amyloid plaques, amyloid-beta 42, intranasal infection, persistent infection, mouse model
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cell Line, Female, Humans, Mice, Inbred BALB C, Peptide Fragments, Amyloid beta-Peptides, Chlamydophila pneumoniae, Chlamydophila Infections, Mice, Plaque, Amyloid
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