P3-223: Caspase activity is inhibited in neuronal cells infected with Chlamydia pneumoniae: Implications for apoptosis in Alzheimer’s disease

Background:  Studies have suggested that apoptosis may contribute to the neuronal cell loss observed in Alzheimer’s disease (AD). Aβ 1-42 has been shown to induce apoptosis in neurons and may be an initiating factor in AD. Caspase is an effector in neuronal apoptosis that could also play a role in AD. However, the extent to which apoptosis contributes to cell death in AD has yet to be delineated. In an earlier study, we identified and isolated  Chlamydia pneumoniae  from brains of patients that had been diagnosed with sporadic AD. These  in vitro studies suggested that neurons infected with  C. pneumoniae  are resistant to apoptosis, and that the processing or production of APP into Aβ1-42 was increased by the infection. In addition, we have developed a novel murine model in which non-transgenic mice infected with  C. pneumoniae  formed deposits of amyloid in areas of the brain most affected in Alzheimer’s disease. Interestingly, some of the neurons in these areas showed a high level of Aβ 1-42 immunoreactivity, and these neurons did not appear to be undergoing apoptosis.  Objective:  The focus of the current studies was to delineate whether caspase is activated following a  C. pneumoniae  infection in neuronal cells.  Methods:  Apoptosis was experimentally induced by staurosporine in uninfected SK-N-MC cells and cells infected with  C. pneumoniae.  Caspase activity was analyzed using the Apo-ONE caspase 3/7 assay (Promega).  Results:  We found that staurosporine induced an increase in caspase 3/7 activity in both infected and uninfected cells, however the staurosporine-treated infected cells had lower activity than even the basal activity of uninfected cells. These data were consistent with immunocytochemistry, which showed decreased labeling by antibodies that recognize cleaved (active) caspase 3 in the infected cells.  Conclusions:  These results suggest that inhibition of apoptosis by suppression of caspase 3/7 activity, and/or by decreasing levels of active caspase 3, may be mechanisms by which  C. pneumoniae  can sustain a persistent infection in the host and optimize its intracellular environment. In this way,  C. pneumoniae  may participate in the pathogenesis characteristic of Alzheimer’s disease.