Clinical, cell biological and molecular biological research of ALS/parkinsonism-dementia complex of the Kii peninsula of Japan

(1)确立了日本Kii半岛肌萎缩性侧索硬化症/帕金森病-痴呆复合体（Kii ALS/PDC）的疾病概念。我们揭示了Kii ALS/PDC的流行病学、神经学特征以及神经生理学、神经放射学和神经病理学的表现。Kii ALS/PDC被证实是中枢神经系统（CNS）神经原纤维缠结（nft）的一种tau病，这是关岛ALS/PDC的一个特定特征。(2)基因分析我们正在进行DNA分析，寻找Kii ALS/PDC的致病基因。(3)在Kii半岛非神经退行性疾病患者中未观察到tau蛋白NFT的细胞生物学研究，提示NFT是Kii ALS/PDC的特异性特征。采用免疫组织化学和western blot方法对Kii ALS/PDC患者脑内积累的Tau蛋白进行分析。同种型。Kii ALS/PDC的tau蛋白由3和4个重复tau组成。Tau蛋白在与阿尔茨海默病相同的位点高度磷酸化。

(1)Establishment of the disease concept of amyotrophic lateral sclerosis/ parkinsonism- dementia complex of the Kii peninsula of Japan ( Kii ALS/PDC).We revealed the epidemiology, neurological features, and neurophysiological, neuroradiological and neuropathological findings of Kii ALS/PDC. Kii ALS/PDC was proved to be a tauopathy presenting neurofibrillary tangles (NFTs) in the central nervous system (CNS), which are a specific feature of ALS/PDC in Guam.(2)Genetic analysisWe are performing a DNA analysis and searching the causative gene of Kii ALS/PDC.(3)Cell biological study of tau proteinNFTs were not observed in the residents with non-neurodegenerative disease in Kii peninsula, so NFT was revealed to be a specific feature of Kii ALS/PDC.Tau protein, which is accumulated in the brains of Kii ALS/PDC, was analyzed by immunohistochemical and western blot method.The isoform. of tau protein of Kii ALS/PDC was composed of 3 and 4 repeat tau. Tau protein was hyper-phospholilated at the same sites of that of Alzheimer's disease.