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

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ID: 117554
2015
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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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taniguchi-watanabe2015actabiochemical Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
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;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;
Journal acta neuropathologica
Year 2015
DOI
doi:10.1007/s00401-015-1503-3
URL
https://link.springer.com/article/10.1007/s00401-015-1503-3
Keywords
pathology neurosciences

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