Depletion of microglia with CSF1R inhibitor prevents tau aggregation in the mouse model Thy1P301S

Background Neuroinflammation and microglia proliferation are central in Alzheimer’s disease pathology. However, the role of microglia in the accumulation and spreading of plaques and tau tangles is not yet well understood. Method In this study, we depleted the microglia population in the brain of Alzheimer’s disease (APP PS1) tauopathy (Thy1P301S) and dual pathology (APPPS1 Thy1P301S) mice models using a colony stimulating factor 1 receptor (CSF1R) inhibitor to achieve microglia ablation. Consequences of compound treatment on brain pathology were analyzed. Result Reduced number of microglia cells in the brain was successfully achieved in the mouse model Thy1P301S. In a chronic treatment study of 3 months, mice treated with the CSF1R inhibitor showed a significant decrease in tau aggregation and deposition compared to the control group. Conclusion Here we show that inhibition of microglia proliferation induces attenuation of tau pathology. This work demonstrates that intervention on microglia is a potential therapeutic approach in Alzheimer’s disease.