Detection of bacterial antigens and Alzheimer’s disease-like pathology in the central nervous system of BALB/c mice following intranasal infection with a laboratory isolate of Chlamydia pneumoniae
Open accessAbstract
Pathology consistent with that observed in Alzheimer's disease (AD) has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn) isolated from an AD brain (96-41). In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi). Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months. Viable Cpn was recovered from olfactory bulbs of 3 of 3 experimentally infected mice at 1 and 3 months pi, and in 2 of 3 mice at 4 months pi. In contrast, in cortical tissues of infected mice at 1 and 4 months pi no viable organism was obtained. At 3 months pi, only 1 of 3 mice had a measurable burden of viable Cpn from the cortical tissues. Mock-infected mice (0 of 3) had no detectable Cpn in either olfactory bulbs or cortical tissues. These data indicate that the AR-39 isolate of Cpn establishes a limited infection predominantly in the olfactory bulbs of BALB/c mice. Although infection with the laboratory strain of Cpn promotes deposition of amyloid beta, this appears to resolve following reduction of the Cpn antigen burden over time. Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41. These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.
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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 [17]
The Results section (page unavailable) reports C. pneumoniae antigen in olfactory bulbs at 1 and 3 months and viable organisms in olfactory bulbs at 1, 3, and 4 months after intranasal infection. It does not report detection in the olfactory mucosa, so that part of the attributed claim is unsupported. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe 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 [17]
The Results sections report C. pneumoniae antigen in the brain at one month after infection and viable organisms in the olfactory bulbs at one and three months; viable organisms were recovered from cerebral tissue in one mouse at three months. The paper does not report CNS infection at one week, so it supports the months-long portion of the cited range but not its one-week endpoint. No page number is available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredControl 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 [50]
The Results section (‘Identification and distribution of amyloid antigen in the central nervous system’; page unavailable) reports a low but detectable number of amyloid-immunoreactive sites in mock-infected control mice at 2, 3, and 4 months. It does not describe those deposits as diffuse, so it supports their presence but not the claimed morphology. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe 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 [17]
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 [17]
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 [50]
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 [17]
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- Authors
- Little, C. S., Joyce, T. A., Hammond, C. J., Matta, H., Cahn, D., Appelt, D. M., & Balin, B. J.
- Affiliations
- Philadelphia College of Osteopathic Medicine (US)
- Corresponding author
- Little, Christopher S.
- Venue
- Frontiers in Aging Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2014-12-05
- Volume
- 6
- Pages
- 304-304
- ISSN
- 1663-4365 (ISSN-L)
- PMC
- PMC4257355
- OpenAlex
- W2080023640
- Cited by
- 71
- References
- 4
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 1 · 2022: 7 · 2021: 7 · 2020: 9 · 2019: 9 · 2018: 9 · 2017: 5 · 2016: 7 · 2015: 5
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Aging Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons - PCOM (Philadelphia College of Osteopathic Medicine) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Osteopathic Heritage Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- Chlamydia pneumoniae, Alzheimer's disease, amyloid-beta deposition, olfactory bulb, intranasal infection, BALB/c mice, central nervous system infection, bacterial antigen detection
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