Presentation
Increased AB 1-42 amyloid processing into oligomers in astrocytes and neuronal cells infected with Chlamydophila (Chlamydia) pneumoniae
Society for Neuroscience 2008 Annual Meeting
(2008)
Abstract
Previously, our laboratory identified Chlamydophila (Chlamydia) pneumoniae (Cpn) in autopsied sporadic AD brains. Our BALB/c mouse model has yielded infection-induced amyloid plaques similar to those found in AD, and we have also demonstrated that Cpn infection of neuronal cells inhibited apoptotic pathways of cell death. The current investigation addresses the processing of the B amyloid precursor protein (BAPP) into AB 1-42 in astrocytes and neuronal cells infected in vitro with Cpn. The study was initiated to determine if high molecular weight AB-derived diffusible ligands (ADDLs) were produced following infection.
We hypothesized that infection of astrocytes and neuronal cells with Cpn triggers increased cleavage of the beta amyloid precursor protein (BAPP) into AB1-42 oligomers, thereby associating Cpn infection with the formation of toxic AB amyloid species that may contribute to the pathology of Alzheimer’s disease.
To address our hypothesis, human neuroblastoma cells (SK-N-MC- HTB-10) and murine astrocytes (C8-DIA) were infected in vitro with the respiratory strain AR39 Cpn. At 24 to 72 hours post-infection, amyloid processing into AB 1-42 was analyzed and quantitated using immunocytochemistry, Western blotting and ELISA assays.
Our results indicated that intracellular amyloid processing was induced in astrocytes and neuronal cells infected by Cpn; both infected cell types yielded cytoplasmic labeling of presumptive AΒ 1-42 oligomers that was increased relative to uninfected cells. The ELISA assay revealed that in neuronal cell lysates, AB 1-42 in the infected cells was increased 3 to 16-fold over the uninfected cells from 24 to 72 hrs post-infection, however in lysates of astrocytes, the infection-induced change in AB 1-42 was much less robust at 72hr post-infection. Western blot analysis confirmed an increase in higher molecular weight (>50kDa) AB 1-42 in the infected neuronal cell lysates at all time points post-infection, whereas in astrocyte lysates, AB 1-42 was increased at 24 hrs but unchanged at 48 -72 hrs post-infection, compared to uninfected controls.
These data suggest that infection of astrocytes and neuronal cells with Chlamydophila (Chlamydia) pneumoniae affects the processing of BAPP into AB1-42 higher molecular weight species presumably representing ADDLs. Therefore, these studies and previous research reported by our laboratory support the implication of Cpn as a pathogenic agent that can perpetuate the production of neurotoxic amyloid found in Alzheimer's disease.
Disciplines
Publication Date
November, 2008
Location
Washington, DC
DOI
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=9beab5e3-b0d1-48e9-a292-2571d3ed1dba&cKey=c16478e8-3e45-4179-9cc5-9e205b7872c1&mKey=%7bAFEA068D-D012-4520-8E42-10E4D1AF7944%7d
Citation Information
Denah M. Appelt, E K Ruszak, Marcus G. Bell and Brian J. Balin. "Increased AB 1-42 amyloid processing into oligomers in astrocytes and neuronal cells infected with Chlamydophila (Chlamydia) pneumoniae" Society for Neuroscience 2008 Annual Meeting (2008) Available at: http://works.bepress.com/brian_balin/109/