Chapman J, Cervenáková L, Petersen R B, Lee H S, Estupinan J, Richardson S, Vnencak-Jones C L, Gajdusek D C, Korczyn A D, Brown P, Goldfarb L G
Clinical Neurogenetics Unit, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4129, USA.
Neurology. 1998 Aug;51(2):548-53. doi: 10.1212/wnl.51.2.548.
The APOE genotype has been shown to influence the risk of developing sporadic and familial AD. This effect is isoform-dependent, the APOE epsilon4 allele increasing susceptibility and the APOE epsilon2 allele providing protection. Amyloid formation is an important part of the pathogenesis in AD as well as in spongiform encephalopathies; apoE deposition in amyloid plaques has been documented in both conditions.
We examined the frequency of the APOE alleles in patients with various forms of transmissible spongiform encephalopathies, or prion diseases, including sporadic and iatrogenic Creutzfeldt-Jakob disease; familial Creutzfeldt-Jakob disease associated with PRNP 178N/129V and 200K/129M point mutations and a 24-nucleotide repeat expansion; fatal familial insomnia caused by the 178N/129M mutation; Gerstmann-Sträussler-Scheinker disease associated with 102L/129M mutation; and kuru.
None of the groups we studied had a significant excess of APOE epsilon4 allele when compared with appropriate controls.
Our results do not support the contention that the APOE epsilon4 allele is a risk factor for developing Creutzfeldt-Jakob disease or related disorders.
已证明载脂蛋白E(APOE)基因型会影响散发性和家族性阿尔茨海默病(AD)的发病风险。这种影响具有异构体依赖性,APOE ε4等位基因会增加易感性,而APOE ε2等位基因则提供保护作用。淀粉样蛋白形成是AD以及海绵状脑病发病机制的重要组成部分;在这两种病症中均已记录到淀粉样斑块中有载脂蛋白E沉积。
我们检测了各种形式的传染性海绵状脑病(即朊病毒病)患者中APOE等位基因的频率,这些疾病包括散发性和医源性克雅氏病;与PRNP 178N/129V和200K/129M点突变以及24个核苷酸重复扩增相关的家族性克雅氏病;由178N/129M突变引起的致死性家族性失眠症;与102L/129M突变相关的格斯特曼-施特劳斯勒-谢inker病;以及库鲁病。
与适当的对照组相比,我们研究的所有组中APOE ε4等位基因均无显著过量。
我们的结果不支持APOE ε4等位基因是克雅氏病或相关疾病发病风险因素的观点。