title: Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration.
abstract: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative diseases that are characterized by intracytoplasmic aggregates of hyperphosphorylated tau with four microtubule-binding repeats. Although PSP and CBD have distinctive pathological features, no biochemical difference in aggregated tau has been identified. In this study, we examined the brains of eight patients with PSP, six patients with CBD, and one atypical case with pathological features of both CBD and PSP. On immunoblots of sarkosyl-insoluble brain extracts, a 33kDa band predominated in the low molecular weight tau fragments in PSP, whereas two closely related bands of approximately 37kDa predominated in CBD. Immunoblots of the atypical case showed both the 33kDa band and the 37kDa doublet. Protein sequencing and immunochemical analyses showed that the 33kDa band and the 37kDa doublet consisted of the carboxyl half of tau with different amino termini. These results suggest that, despite the identical composition of tau isoforms, different proteolytic processing of abnormal tau takes place in these two diseases. Such a biochemical divergence may be related to the neuropathological features of these diseases.
authors.affiliation: Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Setagaya-ku, Tokyo, Japan. aria@prit.go.jp
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Arai
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Nonaka
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Ishiguro
authors.forename: Shuji
authors.initials: S
authors.lastname: Iritani
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Eizo
authors.initials: E
authors.lastname: Iseki
authors.forename: Saburo
authors.initials: S
authors.lastname: Yagishita
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Oda
authors.forename: Akihide
authors.initials: A
authors.lastname: Mochizuki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism*; D024801:Tauopathies / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016875:tau Proteins