Epidemiological, clinicopathological and molecular genetic : study on amyotrophic lateral sclerosis / parkinsonism-dementia complex of the kii peninsula of Japan (kii ALS/PDC)

肌萎缩性侧索硬化症（ALS）是一种顽固性神经退行性疾病，也是一种地方性疾病，帕金森-痴呆复合体（PDC）在西太平洋的关岛岛和日本纪伊半岛南部海岸的发病率非常高。西太平洋肌萎缩侧索硬化症和PDC的神经病理学特征是在大脑中存在许多神经原纤维缠结（nft）。广泛的调查未能阐明ALS和PDC高积累的原因，到1980年有报道称它们明显下降。我们在肌萎缩性侧索硬化症高发地区之一的Hohara村进行了实地调查，发现1980年后肌萎缩性侧索硬化症和PDC的发病率持续居高不下。我们发现21例ALS/PDC发生于1985年和1997年。ALS和PDC同时发生在单个患者或单个家庭成员中。超过70%的患者有ALS/PDC家族史。我们对6例ALS/PDC患者进行了神经病理学检查，其中包括Kii半岛的首例PDC尸检病例。ALS和PDC表现出相似的结果，ALS病理和许多nft。这些观察结果表明，Kii半岛的ALS和PDC是一种单一疾病的不同临床表现。在12例ALS/PDC患者中进行的基因分析中，apoE多态性与阿尔茨海默病的风险、CYP2D6多态性与帕金森病的风险、tau多态性与进行性核上性麻痹的风险、家族性ALS的SOD1基因突变以及与17号染色体相关的额颞叶痴呆的tau基因突变均未发现任何异常。更多阐明候选基因的研究正在进行中。

Amyotrophic lateral sclerosis (ALS), an obstinate neurodegenerative disease and an endemic disease, parkinsonism-dementia complex (PDC) accumulate in very high prevalence on the Guam island and the southern coast of the Kii peninsula of Japan in the western Pacific. The western Pacific ALS and PDC are neurothologically characterized by presence of many neurofibrillary tangles (NFTs) in the brain. Extensive investigations failed to clarify the cause of high accumulation of ALS and PDC, and markedly decline of them by 1980 was reported. We had a field survey in the Hohara village, one of the high prevalence ALS foci, and found continuing high incidence rates of ALS and PDC after 1980. We found 21 cases of ALS/PDC which developed during 1985 and 1997. ALS and PDC occurred simultaneously in a single patient or members of a single family. More than 70% of the patients had a family history of ALS/PDC. We examined 6 cases of ALS/PDC neuropathologically, including the first autopsy case of PDC of the Kii peninsula. Both ALS and PDC showed similar findings, the ALS pathology and many NFTs. These observations suggest that ALS and PDC of the Kii peninsula are different clinical manifestations of a nosologically single disease. Gene analyses done in 12 ALS/PDC patients for apoE polymorphism as a risk of Alzheimer's disease, CYP2D6 polymorphism as a risk of Parkinson's disease, tau polymorphism for a risk of progressive supranuclear palsy, SOD1 gene mutation of familial ALS, and tau gene mutation of frontotemporal dementia linked to chromosome 17 failed to reveal any abnormalities. More studies to clarify the candidate gene(s) are in progress.