Itoh Nobuo, Ishiguro Koichi, Arai Hiroyuki, Kokubo Yasumasa, Sasaki Ryogen, Narita Yugo, Kuzuhara Shigeki
Department of Neurology, Mie University School of Medicine, Tsu, Japan.
J Neuropathol Exp Neurol. 2003 Jul;62(7):791-8. doi: 10.1093/jnen/62.7.791.
Amyotrophic lateral sclerosis/parkinsonism-dementia complex of the Kii peninsula (Kii ALS/PDC) is a neurodegenerative disorder endemic to natives in the southern coast area of the Kii peninsula of Japan. The disorder closely resembles Guamanian ALS/PDC clinically and neuropathologically. The characteristic neuropathological finding is abundant neurofibrillary tangles (NFTs) without amyloid deposition. To elucidate the biochemical properties of hyperphosphorylated tau protein, the major component of the NFTs, we examined Kii ALS/PDC brains by immunoblotting and immunohistochemical analysis using well-characterized anti-tau antibodies specific to phosphorylation-dependent or -independent epitopes. Hyperphosphorylated tau in Kii ALS/PDC had phosphorylated epitopes common to tau of paired helical filaments (PHFs) in Alzheimer disease (AD): immunoblot showed triplet bands composed of 6 tau isoforms. Ultrastructurally, NFTs revealed a twisted filamentous shape similar to PHF of AD. The biochemical properties of its phosphorylated tau protein and the ultrastructural characteristics of the NFTs of Kii ALS/PDC are very similar, if not identical, to PHF tau in AD, although they are different taupopathies.
纪伊半岛肌萎缩侧索硬化症/帕金森病-痴呆综合征（纪伊ALS/PDC）是一种在日本纪伊半岛南部沿海地区的当地居民中流行的神经退行性疾病。该疾病在临床和神经病理学上与关岛ALS/PDC极为相似。其特征性的神经病理学发现是存在大量神经原纤维缠结（NFTs）而无淀粉样蛋白沉积。为了阐明NFTs的主要成分——过度磷酸化tau蛋白的生化特性，我们使用针对磷酸化依赖性或非依赖性表位的特异性良好的抗tau抗体，通过免疫印迹和免疫组织化学分析对纪伊ALS/PDC患者的大脑进行了检查。纪伊ALS/PDC中的过度磷酸化tau具有与阿尔茨海默病（AD）中配对螺旋丝（PHF）的tau共同的磷酸化表位：免疫印迹显示由6种tau异构体组成的三联条带。在超微结构上，NFTs呈现出与AD的PHF相似的扭曲丝状形态。尽管纪伊ALS/PDC和AD是不同的tau蛋白病，但其磷酸化tau蛋白的生化特性以及纪伊ALS/PDC的NFTs的超微结构特征与AD中的PHF tau非常相似，甚至可以说是相同的。
