Evaluation of the olfactory neuro-epithelium and limbic system from cadaveric Alzheimer’s disease and non-Alzheimer’s disease brains for evidence of pathology and Chlamydia pneumoniae infection
Date of Award
7-2023
Degree Type
Thesis
Degree Name
Master of Science in Biomedical Sciences
First Advisor
Brian Balin, PhD
Second Advisor
Denah Appelt PhD
Third Advisor
Scott Little, PhD
Abstract
Background: Alzheimer’s disease (AD), the most prominent form of neurodegeneration, is defined by pathology consisting primarily of beta-amyloid (Ab) plaques and Tau neurofibrillary tangles. Pathogenesis of AD begins in the limbic regions of the brain, wherein AD pathology is observed prior to manifesting in any other brain regions. Intriguingly, infection with Chlamydia pneumoniae (Cpn) has been observed in AD brains and correlated to AD pathology. This current study examines the presence of AD pathology and infection with Cpn in the limbic regions of AD and non-AD brain tissues. In an animal model, intranasal infection of Cpn resulted in infection of the olfactory neuro-epithelia and limbic areas of the brain, supporting this route of infection as a potential precursor to pathology in AD. We hypothesize that infection with Cpn can disseminate via the olfactory neuro-epithelia to the olfactory bulbs and tract with eventual infection of the limbic system in the AD brain. The presence of Cpn antigens promotes inflammation and the development of AD pathology in these brain regions will strengthen our understanding of infection with Cpn as a risk factor for AD pathogenesis.
Materials and Methods: Brain tissues were obtained from cadavers donated to PCOM from the Human Gifts Registry for anatomical dissection. Cadaveric tissue samples of the limbic system and the olfactory neuro-epithelia were collected and analyzed using immunohistochemistry (IHC) for the presence of AD pathology, Ab and Tau, and infection with Cpn. Five paired samples from different limbic areas and olfactory neuroepithelia, sex-matched, were analyzed. The presence of Ab plaques was quantified using percent area of the plaques. Tau and Chlamydial immunoreactivity were analyzed semiquantitatively.
Results: We observed increased amounts of Ab and Tau in AD versus non-AD brains. The presence of Chlamydial antigens has been observed in both AD and non-AD brains and olfactory neuro-epithelia, but increased amounts of Chlamydial immunoreactivity appeared in the AD brains and AD neuro-epithelia as compared to the non-AD samples.
Conclusions: We have observed the presence of Chlamydial antigens along with pathology consisting of Ab plaques and Tau neurofibrillary tangles within the limbic system and olfactory neuro-epithelia of AD brains. Given the presence of Cpn in olfactory neuro-epithelia, our hypothesis of intranasal infection as a precursor to infection in the limbic system is supported. More data on infection of the olfactory neuro-epithelia and corresponding brain regions demonstrating pathology will further strengthen the hypothesis. Generating a more extensive data set may enable us to further characterize infection with Cpn as a significant risk factor for AD.
Recommended Citation
Connolly, Matthew, "Evaluation of the olfactory neuro-epithelium and limbic system from cadaveric Alzheimer’s disease and non-Alzheimer’s disease brains for evidence of pathology and Chlamydia pneumoniae infection" (2023). PCOM Biomedical Studies Student Scholarship. 225.
https://digitalcommons.pcom.edu/biomed/225