Chlamydia Pneumoniae Induction of ADDL Peptides in Monocytes and Neuronal Cells May Lead to Toxic Amyloid Production in Alzheimer's Disease
Date of Award
Master of Science in Biomedical Sciences
Denah Appelt, PhD
Brian J Balin, PhD
Susan Hingley, PhD
Marcus Bell, PhD
Amyloid-~ derived diffusible ligands (ADDLs) are soluble, non-fibrillar 1 oligomers that are thought to affect memory by interrupting synaptic functioning. One of the components of these oligomers, amyloid ~ (A~) 1-42, has been shown to be increased in vivo as well as in vitro in neuronal cells, monocytes and astrocytes in the presence of Chlamydia pneumoniae (CP) infection. The study presented in this manuscript attempts to fmiher characterize the relationship between CP infection, A~ production and oligomer formation. Neuronal cells and monocytes were infected with CP for 24,48 and 72 hours and were evaluated for A~ and ADDL production levels by immunocytochemistry, western blot analysis and ELISA. Since a shift in the ratio of A~40 and A~42 has been implicated in ADDL formation, this study was designed to investigate the influence of CP infection on production of both forms of A~. The results of these experiments indicated that CP infection did influence production/processing of A~ in both neurons and monocytes. Immunoreactivity of both forms of A~ and A~ oligomers was increased in infected monocytes compared to uninfected cells at all time points. While in neuronal cells, the same increase in immunoreactivity of A~ forms and A~ oligomers in infected cells occurred at 24 and 48 hours. At 72 hours post-infection though, A~ oligomer labeling was indistinguishable between infected and uninfected neurons. Monocytes at 48 and 72 hours post-infection with CP exhibited increased labeling of AP and ADDLs by western blot and ELISA, whereas infected neurons demonstrated less consistent AP and ADDL labeling utilizing these same techniques. These results indicate that production/processing of AP may be differentially influenced by CP infection in neuronal cells when compared to monocytes. Collectively, results from this study indicate the possibility of CP infection exelis an effect on AP production/processing in neurons and monocytes. Several studies have indicated that AP aggregation into ADDLs may damage neuronal synapses, resulting in the interruption of long-term memory potentiation, which is a characteristic observed in Alzheimer's disease (AD) patients. These studies suppOli our hypotheses that CP impacts AP production/processing and AP oligomer formation as observed in AD pathogenesis.
McCourt, Laura E., "Chlamydia Pneumoniae Induction of ADDL Peptides in Monocytes and Neuronal Cells May Lead to Toxic Amyloid Production in Alzheimer's Disease" (2011). PCOM Biomedical Studies Student Scholarship. 35.