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)是一种顽固的神经退行性疾病，也是一种地方性疾病，帕金森病-痴呆复合体(PDC)在西太平洋的关岛和日本基伊半岛南海岸积聚着非常高的发病率。西太平洋ALS和PDC的神经学特征是脑中存在许多神经原纤维缠结(NFT)。广泛的研究未能弄清ALS和PDC高度积累的原因，据报道，到1980年，ALS和PDC显著下降。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的发病率一直居高不下。我们发现了在1985-1997年间发生的21例ALS/PDC。ALS和PDC同时发生在单个患者或单个家庭成员中。70%以上的患者有ALS/PDC家族史。我们对6例ALS/PDC进行了神经病理检查，其中包括第一例Kii半岛PDC尸检病例。ALS和PDC都有相似的表现，ALS病理和许多NFT。这些观察表明，Kii半岛的ALS和PDC是同一种单一疾病的不同临床表现。对12例ALS/PDC患者进行的载脂蛋白E基因多态与阿尔茨海默病的风险、CYP2D6基因多态与帕金森病的风险、tau基因多态与进行性核上性瘫痪的风险、家族性ALS的SOD1基因突变以及与17号染色体连锁的额颞部痴呆的tau基因突变的基因分析均未发现任何异常。更多澄清候选基因(S)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.