A new mouse model reproduces the subtype-specific pathological transmission of tau protein

Masato Hosokawa (former principal researcher at Tokyo Institute of Urban Medicine, Faculty of Pharmacy, Fukuoka University), Masami Masuda-Suzukake, Hiroshi Shitara, Aki Shimozawa, Genjiro Suzuki, Hiromi Kondo, Takashi Nonaka, Masato Hasegawa (TMIMS) William Campbell (Telarray Diagnostics) And Tetsuaki Arai (University of Tsukuba) reported a new mouse model in which the subtype-specific transmission of tau protein in the "brain"

Bovine degenerative diseases such as Alzheimer's disease (AD), cortical basal degeneration (CBD) and Pick's disease (PiD) are believed to be caused by abnormal accumulation of tau protein in neurons and glial cells leading to neurodegeneration and leading to dementia

In the mouse model produced in the past, the mouse brain injected with the insoluble part of the brain of AD patients can induce the accumulation of 4R tau, but not the accumulation of 3R tau

First, Hosokawa and his colleagues created a new type of mouse expressing endogenous 6-isoform tau protein to overcome the shortcomings of the previous experimental mouse model injected with tau protein

Next, Hosokawa and his colleagues extracted detergent-insoluble parts from the autopsy brains of AD, CBD, and PiD patients, and injected the tau fibrils contained in these parts into the striae of tau 3R/4R mice.

In addition, in the brains of mice injected with AD-tau fibrils, after phosphorylated tau antibody (AT8) staining, the pathology of tau aggregation in the striatum at the injection site increased over time, and the pathology of tau aggregation spread to the cerebral cortex

Finally, when the brains of mice injected with PiD tau fibrils were examined in detail, globular tau accumulation pathology was observed, but this was not observed when AD or CBD tau fibrils were injected

Gotaro Hosokawa and his colleagues next studied the accumulation of tau protein in mice after injection of human tau protein extracted from AD patients

This experiment confirmed the following properties of prion-like τ: (1) Abnormal τ has the ability to cause isoform-specific, seed-dependent aggregation, (2) Abnormal τ has the ability to propagate, and (3) Human τ fibers injected into the brain can induce endogenous Sexual accumulation of mouse τ across species

DOI

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