Neurodegenerative diseases with tau protein deposition are collectively known as tauopathies, and a prion-like propagation hypothesis has recently been proposed for their pathogenesis. Pick's disease is one of these diseases that shows the accumulation of only 3-repeat tau isoform (3R tau). However, it has been impossible to recapitulate the pathology of Pick's disease in adult wild-type mice because they do not express 3R tau.
In this study, we attempted to generate a mouse model of 3R tau accumulation by intracerebral injection of recombinant 3R tau aggregates into tau knock-in mice expressing 3R tau (Hosokawa et al. Brain 2022). Recombinant tau aggregates consisting of full-length 3R tau or tau fragments (244-391a.a.) were injected into the hippocampus of tau knock-in mice, and tau pathology was analyzed by immunohistochemistry.
As a result, AT8-positive tau pathology was observed in mice injected with tau aggregates, and tau pathology spread from the injection sites to the other brain regions over time. These results indicate that 3R tau accumulation can be induced by intracerebral injection of synthetic tau seeds into tau knock-in mice by a prion-like mechanism.