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Dissertation
Chlamydia pneumoniae: an emerging pathogen in Alzheimer's disease
Doctor of Philosophy (Ph.D.), Allegheny University of the Health Sciences
Aug 1998
DOI:
https://doi.org/10.17918/00007970
Abstract
The following work was completed in order to assess 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 seemed to suggest that infection with the organism might be associated with the disease. Nucleic acids prepared from those samples were screened by 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 analyses of non-AD brain tissues for C. pneumoniae were negative for the bacterium. Culture analyses of a subset of affected brain tissues for C. pneumoniae were strongly positive, while identically performed analyses of non-AD brain tissues were negative. RT-PCR assays using RNA from affected areas of AD brains confirmed that transcripts from two important C. pneumoniae genes, ompA and 16S rRNA, were present in those samples but not in controls. Immunohistochemical examination identified C. pneumoniae within pericytes, microglia, and astroglia in AD brains but not in controls. Further immunolabeling studies confirmed the organism's intracellular presence primarily in areas of neuropathology in the AD brain. In situ hybridization revealed that pericytes and glial cells in areas which demonstrated AD pathology were immunoreactive with the probe while those areas without neuropathology were not immunoreactive. Thus, C. pneumoniae is present, viable, and transcriptionally active in areas of neuropathology in the AD brain, suggesting that infection with the organism is a risk factor for late-onset AD. (Abstract shortened by UMI.).
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Details
- Title
- Chlamydia pneumoniae
- Creators
- Edward James Arking
- Contributors
- Brian J. Balin (Advisor) - Drexel University, Allegheny University of the Health Sciences (1996-1998)
- Awarding Institution
- Allegheny University of the Health Sciences
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Allegheny University of the Health Sciences; Philadelphia, Pennsylvania
- Number of pages
- 170 unnumbered pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Allegheny University of the Health Sciences (1996-1998); School of Medicine (1996-1998); Pathology (and Laboratory Medicine) [Historical]
- Other Identifier
- 991021889015204721