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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.

Publication Date

2007

Disciplines

Bacterial Infections and Mycoses | Nervous System Diseases | Neurology

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
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