This study investigates the transmission and spreading of tauopathy in transgenic mice. It shows that injecting brain extract from mice expressing mutant human tau (P301S) into transgenic mice expressing wild-type human tau induces the formation and spread of hyperphosphorylated tau filaments. The study used two transgenic mouse lines, ALZ17 (expressing the longest human tau isoform) and P301S (expressing the 383 amino acid tau isoform with the P301S mutation). Injection of P301S brain extract into ALZ17 mice resulted in the appearance of tau filaments and pathological changes in neighboring brain regions. The pathology spread to various brain areas, including the hippocampus, cerebral cortex, and other regions, indicating active spreading rather than passive diffusion. The study also found that insoluble tau species were more effective in inducing tau aggregation than soluble ones. Additionally, the presence of human tau in the injected material was essential for the induction of filamentous tauopathy. The findings suggest that tauopathy can be transmitted between transgenic mouse lines and that the molecular species responsible for transmission may differ from those causing neurodegeneration. The study also highlights the potential for experimental models to investigate the spread of tau pathology and its similarity to prion diseases. The results demonstrate that the transmission of tauopathy can occur through the spread of filamentous tau pathology in the brain, and that this process is time- and region-dependent. The study provides insights into the mechanisms of tau pathology spread and the potential for therapeutic interventions targeting tau aggregation.This study investigates the transmission and spreading of tauopathy in transgenic mice. It shows that injecting brain extract from mice expressing mutant human tau (P301S) into transgenic mice expressing wild-type human tau induces the formation and spread of hyperphosphorylated tau filaments. The study used two transgenic mouse lines, ALZ17 (expressing the longest human tau isoform) and P301S (expressing the 383 amino acid tau isoform with the P301S mutation). Injection of P301S brain extract into ALZ17 mice resulted in the appearance of tau filaments and pathological changes in neighboring brain regions. The pathology spread to various brain areas, including the hippocampus, cerebral cortex, and other regions, indicating active spreading rather than passive diffusion. The study also found that insoluble tau species were more effective in inducing tau aggregation than soluble ones. Additionally, the presence of human tau in the injected material was essential for the induction of filamentous tauopathy. The findings suggest that tauopathy can be transmitted between transgenic mouse lines and that the molecular species responsible for transmission may differ from those causing neurodegeneration. The study also highlights the potential for experimental models to investigate the spread of tau pathology and its similarity to prion diseases. The results demonstrate that the transmission of tauopathy can occur through the spread of filamentous tau pathology in the brain, and that this process is time- and region-dependent. The study provides insights into the mechanisms of tau pathology spread and the potential for therapeutic interventions targeting tau aggregation.