Prion-like propagation of tau and its animal models

Masato Hosokawa¹⁾²⁾

¹⁾Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
²⁾Dementia Research project, Tokyo Metropolitan Institute of Medical Science

A number of experimental tau injection-propagation mouse models have been generated, but they have failed to reproduce pathologies involving 3-repeat （3R） tau, such as Alzheimer’s disease and Pick’s disease.　To overcome these deficiencies, CRISPR-Cas9 genome editing technology was used to generate new mice expressing endogenous 6-isoform tau.　Mice expressing both physiologically normal amounts of 3R and 4R tau （Tau 3R/4R mice）, as found in the adult human brain were generated.　Sarkosyl-insoluble fraction was extracted from autopsy brains of Alzheimer’s disease, corticobasal degeneration and Pick’s disease patients and tau fibrils in this fraction were injected into the striatum of Tau 3R/4R mice.　Biochemical and immunohistochemical analyses confirmed isoform-specific and seed-dependent accumulation of tau.　Our study reveals some aspects of the prion-like properties of tau.

Address correspondence to Dr. Masato Hosokawa, Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University (8-19-1 Nanakuma, Johnan-ku, Fukuoka 814-0180, Japan)