Prion-like propagation model of tau

Abstract

Abnormal proteins such as tau or a-synuclein that accumulate in brains with dementia have been shown to propagate like prion proteins. However, the expression patterns of tau in the mouse brain are different from those in humans, and the pathogenesis in the animal model of abnormal tau propagation remains incompletely understood. To overcome this problem, a novel mouse showing tau expression patterns similar to those of humans was developed using genome editing techniques. We inoculated the brain of this mouse with a sarkosyl-insoluble fraction containing abnormal tau derived from tauopathy patients and examined the accumulation of tau pathologies. We also performed a detailed analysis of the relationship between the inoculation site and the sites where tau accumulates abnormally by histochemical and neuronal circuitry and elucidated the propagation mechanism of the abnormally accumulated protein. This research is expected to lead to the development of novel drugs for the treatment of dementia using the innovative approach of “inhibition of abnormal protein propagation”.