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

肌萎缩侧索硬化症（ALS）是一种顽固性神经退行性疾病和地方病，帕金森痴呆综合征（PDC）在西太平洋的关岛和日本纪伊半岛南部海岸的发病率非常高。西太平洋ALS和PDC的神经病理学特征是脑中存在许多神经元缠结（NFT）。广泛的调查未能澄清ALS和PDC的高积累的原因，并在1980年显着下降的报告。我们在ALS高发区之一的Hohara村进行了实地调查，发现1980年后ALS和PDC的发病率持续高企。我们发现了21例ALS/PDC的发展过程中，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进行了神经病理学检查，其中包括纪伊半岛的首例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，肌萎缩侧索硬化症和PDC的纪伊半岛是不同的临床表现的疾病分类单一的疾病。对12名ALS/PDC患者进行了基因分析，包括apoE多态性（阿尔茨海默病的风险）、CYP 2D 6多态性（帕金森病的风险）、tau多态性（进行性核上性麻痹的风险）、家族性ALS的SOD 1基因突变和与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。更多的研究来澄清候选基因正在进行中。

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.