Latent cerebral T. gondii infection exacerbates Tauopathy in a mouse model of Alzheimer"s disease.

Brain infections by pathogenic micro-organisms are of growing interest for their role in triggering a damaging inflammation cascade that may exacerbate neurodegenerative processes. Toxoplasmosis is one of the most common infections caused by protozoan parasites, with a world seroprevalence of about 30%. Infection of immuno-competent individuals is characterized by bradyzoite-containing cyst development in the brain, leading to life-long persistent infections. Control of cerebral toxoplasmosis is correlated with the establishment of a sustained low-grade neuroinflammation, characterized by the activation of resident immune cells. Using a mouse model of Alzheimer disease (AD), the Tau22 mouse model of progressive tauopathy, our preliminary results indicate that long-term cerebral T. gondii infection exacerbates hippocampal Tau pathology. We also found that T. gondii infection and the Tau22 background synergizes and potentiates immune responses, notably unique microglia signatures known to be detrimental for neuronal functions. In line, our data suggest that cerebral infection impacts on synapse components in Tau22 mice. Thus, long-term cerebral T. gondii infection precipitates the course of Tau pathology in mice, an aspect that we also currently examine in T. gondii seropositive AD patients.