Prion-like transmission of human tau strains in the mouse brain
Lövestam, S.; Shimozawa, A.; Tarutani, A.; Ohtani, R.; Masuda-Suzukake, M.; Hasegawa, K.; Robinson, A. C.; Saito, Y.; Murayama, S.; Yoshida, M.; Suzuki, H.; Onaya, M.; Hasegawa, M.; Goedert, M.; Scheres, S.
Show abstract
Most neurodegenerative diseases are believed to spread through the brain by prion-like mechanisms, where filamentous protein assemblies self-propagate by templated seeding 1. Distinct conformations of amyloid filaments are thought to provide the physical basis for the strains that lead to different diseases 2. 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 Alzheimers disease or corticobasal degeneration into the brains of wildtype mice leads to the seeded assembly of amyloid filaments made of mouse tau with the same structures as those of the seeds. Thereby, we establish that, like 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.
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