CHRONIC LATENT TOXOPLASMA GONDII INFECTION PRECIPITATES COGNITIVE DECLINE IN A TAU MOUSE MODEL OF DEMENTIA

Neuroimmune dysregulations contribute to the pathophysiology of Alzheimer's Disease (AD). Because pathogens shape the immune system throughout life, their association with AD has been suggested. Increasing evidence supports a role for the prevalent, brain-persisting parasite Toxoplasma gondii (Tg ) in chronic neurological diseases. However, our knowledge of the impact of chronic Tg infection on AD pathology and clinical progression remains sparse. While Tg infection has been examined in constitutive mouse amyloidosis models, its contribution to tau pathogenesis and associated cognitive deficits has not been characterized. Given the temporal relationship between natural Tg infection and AD onset, it seems legitimate to evaluate the effects of a strain of Tg leading to latent infection, on the later development of cognitive deficits associated with tauopathy.
To tackle this question, we combined infection by transgenic Tg (Tg.GRA6-OVA), which results in a persisting and subclinical infection, with a slowly progressive mouse model of tauopathy(tau). Tg-infected THY-Tau22 mouse displayed accelerated tau hyperphosphorylation and insoluble forms. Behavioral, immune and biochemical analyses were performed at a time when non-infected (NI) THY-Tau22 micehave not yet developed cognitive deficits.
We found that Tg-infected THY-Tau22 mice displayed behavioral and cognitive impairments earlier than non-infected tau mice, characterized by disinhibition and impaired task learning, while spatial learning and memory remained preserved. Flow cytometry analyses of brain-isolated immune cells revealed significant alterations in immune cell populations in Tg-infected tau mice compared to non-infected controls.
Together, chronic latent Toxoplasma gondii infection accelerates tau-related cognitive decline through neuroimmune alterations.