title: 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.
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.|Department of Neuropathology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8654, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Taniguchi-Watanabe
authors.affiliation: Department of Psychiatry, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 2-1-1 Amakubo, Ibaraki, Tsukuba, 305-8576, Japan.
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Arai
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Kametani
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nonaka
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Masuda-Suzukake
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors.forename: Airi
authors.initials: A
authors.lastname: Tarutani
authors.affiliation: Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo, 173-0015, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murayama
authors.affiliation: Department of Pathology and Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8551, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Pathology and Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8551, Japan.
authors.forename: Kunimasa
authors.initials: K
authors.lastname: Arima
authors.affiliation: Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Institute of Brain, Behaviour and Mental Health, Clinical and Cognitive Neuroscience Research Group, University of Manchester, Salford Royal Hospital, Salford, M6 8HD, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Robinson
authors.affiliation: Institute of Brain, Behaviour and Mental Health, Clinical and Cognitive Neuroscience Research Group, University of Manchester, Salford Royal Hospital, Salford, M6 8HD, UK.
authors.forename: David M A
authors.initials: DMA
authors.lastname: Mann
authors.affiliation: Department of Neuropathology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8654, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwatsubo
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan. hasegawa-ms@igakuken.or.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001921:Brain / Q000648:ultrastructure; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D015151:Immunoblotting / Q000379:methods*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D016253:Microscopy, Immunoelectron / Q000379:methods; D008875:Middle Aged; D011487:Protein Conformation; D012521:Sarcosine / Q000031:analogs & derivatives / Q000378:metabolism; D020539:Sequence Analysis, Protein / Q000379:methods*; D024801:Tauopathies / Q000145:classification* / Q000378:metabolism* / Q000473:pathology; D014357:Trypsin / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins; C025231:sarkosyl; D014357:Trypsin; D012521:Sarcosine
keywords: Alzheimer; CBD; MAPT; PSP; Pick; Strains; Tau