Abstract
This study aims to quantitate Chlamydia pneumoniae (Cpn) and Aβ amyloid plaques throughout the limbic system in brains from individuals diagnosed with late-onset dementia/Alzheimer’s disease (AD) and non-demented conditions. The amount of deposition of amyloid relative to Cpn may further implicate Chlamydia’s role as a trigger for neuroinflammation leading to the pathology observed in late-onset disease.
Sporadic late-onset Alzheimer’s disease (LOAD) is the most common form of dementia, affecting ~55 million individuals worldwide. Despite the prevalence of the disease the etiology of LOAD remains unknown. In recent years, significant attention has been given to the role of infection in the onset and pathogenesis of late-onset dementia/AD. The Cpn pathogen has been an organism of particular focus since the seminal study by Balin et. al 1998 which found that Cpn DNA was present in 90% of brain samples taken from patients diagnosed with LOAD. Subsequent immunohistochemical (IHC) studies demonstrated that Cpn antigens were present in the frontal and temporal cortices of LOAD brains and that Aβ amyloid plaques found in those brain regions co-localize with areas of Cpn immunoreactivity (Hammond et al 2010).
Sections of the hippocampus and the pre-frontal cortex were dissected from the human cadaver brains that had been donated to the Pennsylvania Human Gifts Registry. The brains were paraffin embedded and sectioned for immunostaining. The brains selected were from those whose death certificates indicated dementia/AD or non-dementia diagnosed with cardiovascular disease. Five sections from the hippocampus and the frontal cortex were immunolabeled with specific antibodies for amyloid plaques and Chlamydial inclusions. The proteins were detected using Abcam’s IHC detection kit and the slides were scanned at 40x magnification. The Cpn inclusions and amyloid plaques were counted in each region using the equivalent total area/section and total count was calculated per mm2.
The counts for amyloid deposits in the anterior hippocampal region of the dementia/AD brain revealed on average 84/mm2 and 117/mm2 Chlamydial inclusions. The counts in the frontal cortex of the dementia/AD brain revealed 266/mm2 and 70/mm2 Chlamydial inclusions. The counts in the non-dementia brain were considerably less for amyloid deposits in the anterior hippocampal region and the frontal cortex averaging between 40/mm2 and 49/mm2, respectively. The Chlamydial inclusion counts were also lower as compared to the dementia/AD brain in the anterior hippocampal region and the frontal cortex averaging 17/mm2 and 14/mm2, respectively.
Brain tissues from the Human Gifts registry provide a valuable resource for experimental analysis. This preliminary study yielded data of an association between amyloid pathology and infection with Cpn from both demented and non-demented aged brains. These data help to support prior work demonstrating a relationship between pathogen association and pathology that may correlate to late-onset disease.
Original language | American English |
---|---|
DOIs | |
State | Published - Apr 2022 |
Event | Experimental Biology 2022 - Philadelphia, PA Duration: Apr 1 2022 → … |
Conference
Conference | Experimental Biology 2022 |
---|---|
Period | 4/1/22 → … |
Disciplines
- Biology