Background: There is emerging evidence supporting the hypothesis that pathogens contribute to the production of β-amyloid (Aβ) associated with Alzheimer disease (AD). We hypothesized that Chlamydia pneumoniae (Cpn) infection of human astrocytes, a metabolizer of Aβ, may propagate AD pathology by modifying the expression and activity of APP-processing secretases. This study examines the effect of Cpn infection of astrocytes on the processing of APP by β-site APP cleaving enzyme (BACE1), which is implicated in Aβ formation.

Materials and Methods: Human astrocytes were infected with Cpn strain AR39 for 24 to 72 hours and assessed by fluorescence microscopy, molecular, and biochemical approaches for the effect of Cpn on the pro-amyloidgenic pathway.

Results: Cpn infection of human astrocytoma cells promotes transcriptional upregulation of BACE1 resulting in altered amyloid cleavage products. While levels of secreted sAPPβ increased in uninfected and infected cells, there is a relatively greater increase in infected cells at 48 hours, which coincided with an increase in BACE1 activity at 48 hours. There is an increase in intracellular labeling for Aβ in infected cells, and an increase in secreted Aβ in uninfected cells from 24 to 48 hours.

Conclusions: Our findings suggest that Cpn infection of astrocytes promotes the pro-amyloidgenic pathway of APP processing. These effects of astrocyte infection provide evidence for a direct link between Chlamydia pneumoniae and AD pathology.