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

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.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Taniguchi-Watanabe S,Arai T,Kametani F,Nonaka T,Masuda-Suzukake M,Tarutani A,Murayama S,Saito Y,Arima K,Yoshida M,Akiyama H,Robinson A,Mann DMA,Iwatsubo T,Hasegawa M

doi

10.1007/s00401-015-1503-3

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

267-280

issue

2

eissn

0001-6322

issn

1432-0533

pii

10.1007/s00401-015-1503-3

journal_volume

131

pub_type

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