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Several studies have suggested an infectious etiology for Alzheimer’s disease (AD). We have been investigating a potential role for both Chlamydia pneumoniae and Herpes simplex virus type 1 (HSV1) in the initiation of sporadic late-onset AD. Our current study focuses on investigation of gene expression using Alzheimer-specific Real-Time PCR microarrays on RNA derived from SKNMC human neuronal cells infected with C. pneumoniae and/or HSV1. There are distinct differences in the patterns of gene regulation by the two pathogens. For example, C. pneumoniae induces expression of genes involved in amyloid production and processing, such as β-amyloid precursor protein (APP), β-site APP-cleaving enzyme 1 (BACE1), a γ-secretase complex protein (nicastrin [NCSTN]), NEDD8 activating enzyme E1 (NAE1), as well as a mitochondria-associated protein (hydroxysteroid (17-β) dehydrogenase 10 [HSD17B10]), α-2-macroglobulin (A2M) and the metallopeptidase ADAM9. Conversely, HSV1 tends to down-regulate expression of many genes, including those encoding a component of the γ-secretase complex (anterior pharynx defective 1 homolog A [APH1A]), low density lipoprotein related proteins (LRP1, LRP6, and LRP8), β-synuclein (SNCB) and ubiquinols (UQCRC1, UQCRC2). Co-infection with C. pneumoniae and HSV-1 produced a greater down-regulation of gene expression than that seen with HSV1 alone for several genes, including APP-like proteins (APLP1, APLP2) and kinases (cell division cycle 2 protein [CDC2], cyclin-dependent kinase [CDK5] and CDC2-related kinase [CDKL1]). Our data indicate that both C. pneumoniae and HSV1 can modulate expression of genes associated with AD, and thus could contribute to AD pathology, however these two pathogens likely act via different pathways. Furthermore, for several genes, co-infection with both C. pneumoniae and HSV1 appears to exacerbate the changes in gene expression seen with HSV1 alone.
Bacterial Infections and Mycoses | Nervous System Diseases | Virus Diseases
Devins, Morgan M.; Zoga, Fiora D.; Balin, Brian J.; Appelt, Denah M.; and Hingley, Susan T., "Infection of neuronal cells by Chlamydia pneumoniae and Herpes simplex virus type 1 alters expression of genes associated with Alzheimer’s disease" (2011). Scholarly Posters. 5.