Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration.
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.
Arai
Tetsuaki
T
Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Setagaya-ku, Tokyo, Japan. aria@prit.go.jp
Ikeda
Kenji
K
Akiyama
Haruhiko
H
Nonaka
Takashi
T
Hasegawa
Masato
M
Ishiguro
Koichi
K
Iritani
Shuji
S
Tsuchiya
Kuniaki
K
Iseki
Eizo
E
Yagishita
Saburo
S
Oda
Tatsuro
T
Mochizuki
Akihide
A
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
D016875:tau Proteins