Download Full Text (26.0 MB)
Background: Several studies have suggested an infectious etiology for Alzheimer's disease (AD). Previously, our laboratory identified Chlamydia pneumoniae (Cpn) from autopsied sporadic AD brains, as well as developed a BALB/c mouse model that demonstrated infection-induced amyloid plaques similar to those found in AD. Hypothesis: We propose that an additional pathogen such as herpes simplex virus type 1 (HSV1), also may be a contributing factor in toin the pathology seen in AD. HSV1, in addition to Cpn, may be triggering the abnormal cleavage of the beta amyloid precursor protein (bAPP) into Ab1-42 , thereby contributing to amyloid plaque formation. Our current study examines amyloid processing following infection of primary and C8-DIA murine astrocytes with Cpn and HSV1. Materials and Methods: Immunocytochemistry and western analysis was used to analyze the outcome of infection by these two pathogens. Results: Cpn infection resulted in an increase in cytoplasmic labeling of Ab 1-42 relative to uninfected cells, while increased nuclear labeling of Ab 1-42 was observed following HSV1 infection. Co-infections with Cpn and HSV1 resulted in amyloid labeling resembling that of HSV1 infection alone, though Ab 1-42 labeling appeared decreased specifically in Cpn-infected cells of the co-infected monolayers. Conclusions: These data suggest that infection of astrocytic cells by HSV1 and (Cpn) alter the processing of bAPP, thereby producing Ab1-42. Therefore, these studies, inaddition to the previous research reported by our laboratory, support an emerging linkage of the infectious processs to the neuropathology characteristic of Alzheimer's disease.
Bacterial Infections and Mycoses | Nervous System Diseases | Neurology
Triplett, Laura R.; Dore, Adam L.; Kralik, Kevin S.; Balin, Brian J.; Hingley, Susan T.; and Appelt, Denah M., "Herpes Simplex Virus 1 and Chlamydophila (Chlamydia) pneumoniae promote Ab 1-42 amyloid processing in murine astrocytes linking an infectious process to Alzheimer's disease" (2007). Scholarly Posters. 4.