This study investigates the transmission and spreading of tauopathy in transgenic mouse models. The researchers used two transgenic mouse lines: ALZ17, which expresses the longest human brain tau isoform (441 amino acids), and P301S, which expresses a 383 amino acid human tau isoform with a mutation causing frontotemporal dementia. They found that injecting brain extracts from P301S mice into ALZ17 mice induced the assembly of wild-type human tau into filaments and the spreading of pathology to neighboring brain regions. The pathology, characterized by silver-positive structures, appeared in the hippocampus and cerebral cortex, spreading over time and distance. The study also showed that insoluble tau species were more effective in inducing tau aggregation compared to soluble tau. Additionally, non-transgenic wild-type mice injected with P301S brain extracts developed filamentous tau pathology, confirming the transmission of tauopathy. These findings suggest that tauopathy can be experimentally transmitted and spread within transgenic mouse models, providing a valuable tool for studying the mechanisms of tauopathy progression and potential therapeutic interventions.This study investigates the transmission and spreading of tauopathy in transgenic mouse models. The researchers used two transgenic mouse lines: ALZ17, which expresses the longest human brain tau isoform (441 amino acids), and P301S, which expresses a 383 amino acid human tau isoform with a mutation causing frontotemporal dementia. They found that injecting brain extracts from P301S mice into ALZ17 mice induced the assembly of wild-type human tau into filaments and the spreading of pathology to neighboring brain regions. The pathology, characterized by silver-positive structures, appeared in the hippocampus and cerebral cortex, spreading over time and distance. The study also showed that insoluble tau species were more effective in inducing tau aggregation compared to soluble tau. Additionally, non-transgenic wild-type mice injected with P301S brain extracts developed filamentous tau pathology, confirming the transmission of tauopathy. These findings suggest that tauopathy can be experimentally transmitted and spread within transgenic mouse models, providing a valuable tool for studying the mechanisms of tauopathy progression and potential therapeutic interventions.