Arai Tetsuaki, Ikeda Kenji, Akiyama Haruhiko, Nonaka Takashi, Hasegawa Masato, Ishiguro Koichi, Iritani Shuji, Tsuchiya Kuniaki, Iseki Eizo, Yagishita Saburo, Oda Tatsuro, Mochizuki Akihide
Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Setagaya-ku, Tokyo, Japan.
Ann Neurol. 2004 Jan;55(1):72-9. doi: 10.1002/ana.10793.
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.
进行性核上性麻痹（PSP）和皮质基底节变性（CBD）是神经退行性疾病，其特征是具有四个微管结合重复序列的高磷酸化tau蛋白在胞浆内聚集。尽管PSP和CBD具有独特的病理特征，但在聚集的tau蛋白中尚未发现生化差异。在本研究中，我们检查了8例PSP患者、6例CBD患者以及1例具有CBD和PSP病理特征的非典型病例的大脑。在对 Sarkosyl 不溶性脑提取物进行免疫印迹时，33kDa条带在PSP的低分子量tau片段中占主导地位，而在CBD中约37kDa的两条密切相关条带占主导地位。非典型病例的免疫印迹显示出33kDa条带和37kDa双峰。蛋白质测序和免疫化学分析表明，33kDa条带和37kDa双峰由具有不同氨基末端的tau蛋白羧基端组成。这些结果表明，尽管tau异构体的组成相同，但在这两种疾病中异常tau蛋白发生了不同的蛋白水解加工。这种生化差异可能与这些疾病的神经病理特征有关。
