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Acta Neuropathologica
Published in: Acta Neuropathologica 2/2016

Open Access 01-02-2016 | Original Paper

Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau

Authors: Sayuri Taniguchi-Watanabe, Tetsuaki Arai, Fuyuki Kametani, Takashi Nonaka, Masami Masuda-Suzukake, Airi Tarutani, Shigeo Murayama, Yuko Saito, Kunimasa Arima, Mari Yoshida, Haruhiko Akiyama, Andrew Robinson, David M. A. Mann, Takeshi Iwatsubo, Masato Hasegawa

Published in: Acta Neuropathologica | Issue 2/2016

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Abstract

Intracellular filamentous tau pathology is the defining feature of tauopathies, which form a subset of neurodegenerative diseases. We have analyzed pathological tau in Alzheimer’s disease, and in frontotemporal lobar degeneration associated with tauopathy to include cases with Pick bodies, corticobasal degeneration, progressive supranuclear palsy, and ones due to intronic mutations in MAPT. We found that the C-terminal band pattern of the pathological tau species is distinct for each disease. Immunoblot analysis of trypsin-resistant tau indicated that the different band patterns of the 7–18 kDa fragments in these diseases likely reflect different conformations of tau molecular species. Protein sequence and mass spectrometric analyses revealed the carboxyl-terminal region (residues 243–406) of tau comprises the protease-resistant core units of the tau aggregates, and the sequence lengths and precise regions involved are different among the diseases. These unique assembled tau cores may be used to classify and diagnose disease strains. Based on these results, we propose a new clinicopathological classification of tauopathies based on the biochemical properties of tau.
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Metadata
Title
Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau
Authors
Sayuri Taniguchi-Watanabe
Tetsuaki Arai
Fuyuki Kametani
Takashi Nonaka
Masami Masuda-Suzukake
Airi Tarutani
Shigeo Murayama
Yuko Saito
Kunimasa Arima
Mari Yoshida
Haruhiko Akiyama
Andrew Robinson
David M. A. Mann
Takeshi Iwatsubo
Masato Hasegawa
Publication date
01-02-2016
Publisher
Springer Berlin Heidelberg
Published in
Acta Neuropathologica / Issue 2/2016
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-015-1503-3

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