Prion-like transmission of human tau strains in the mouse brain

Most neurodegenerative diseases are thought to spread through the brain by prion-like mechanisms, in which filamentous protein assemblies self-propagate by templated seeding¹. Distinct conformations of amyloid filaments may provide the physical basis for the strains that lead to different diseases². However, a central pillar of the prion hypothesis, that strains retain their structural identity upon transmission, has not been demonstrated. Here we show that the injection of tau filaments from the brains of individuals with Alzheimer's disease or corticobasal degeneration into the brains of wild-type mice leads to the seeded assembly of amyloid filaments made of mouse tau with the same structures as those of the seeds. Thus, we show that, similar to prion strains, tau filaments propagate through templated seeding, and that the mouse is a suitable model to study the molecular mechanisms by which distinct tau folds drive disease-specific pathology in the brain.