Neuropathologic variants of sporadic Creutzfeldt-Jakob disease and codon 129 of PrP gene
Neuropathologic variants of sporadic Creutzfeldt-Jakob disease and codon 129 of PrP gene
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DOI：
10.1212/wnl.54.8.1641
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发表时间：
2000-04-25
期刊：
影响因子：
9.9
通讯作者：
Alpérovitch, A
中科院分区：
文献类型：
--
作者：
Hauw, JJ;Sazdovitch, V;Alpérovitch, A
目的：目的探讨朊蛋白（PrP）基因第129密码子蛋氨酸/缬氨酸（Met/瓦尔）多态性在散发性克雅氏病神经病理类型和发病机制中的作用。背景资料：克雅氏病是一种传染性海绵状脑病，其特征是PrP的构象变化和多种PrP沉积在脑中，其中一些聚集成淀粉样斑块。研究方法：作者半定量评估了1994年至1998年期间在法国死亡的70例患者（39例Met/Met，11例Met/瓦尔，20例瓦尔/瓦尔）的神经病理学病变并进行了PrP免疫标记。结果如下：Met/Met病例与Met/瓦尔病例相比，（显著病变，尤其是海马旁回，高PrP负荷，大量淀粉样斑块）和瓦尔/瓦尔病例（年轻患者，病程较长：11.5 +/- 3个月，和明显的神经病理学：严重累及海马结构和基底神经节的严重病变、高PrP负荷、大量局灶性非淀粉样蛋白沉积、罕见淀粉样蛋白斑块）。年龄小于55岁的瓦尔/瓦尔患者的病程特别长（19.9 +/- 7个月），并且同皮质在病理学上首当其冲，表明了明显的多样性。结论：密码子129的多态性调节散发性克雅氏病的表型。瓦尔基因型增强蛋白酶抗性PrP的产生，Met/瓦尔基因型促进其聚集成淀粉样斑块。
Objectives: To determine the contribution of methionine/valine (Met/Val) polymorphism at codon 129 of the prion protein (PrP) gene in the neuropathologic pattern and mechanisms of lesion development in sporadic Creutzfeldt-Jakob disease. Background: Creutzfeldt-Jakob disease is a transmissible spongiform encephalopathy characterized by a conformational change of PrP and a variety of PrP deposits in the brain, some of which aggregate into amyloid plaques. Methods: The authors semiquantitatively assessed neuropathologic lesions and performed PrP immunolabeling in 70 patients (39 Met/Met, 11 Met/Val, 20 Val/Val) who had died in France between 1994 and 1998. Results: Met/Met cases (mild lesions mostly involving the occipital areas, low PrP load, few focal PrP nonamyloid deposits, no amyloid plaques) contrasted with Met/Val cases (marked lesions especially in the parahippocampal gyrus, high PrP load, numerous amyloid plaques) and with Val/Val cases (younger patients, longer course of disease: 11.5 +/- 3 months, and distinct neuropathology: severe lesions heavily involving the hippocampal formation and basal ganglia, high PrP load, numerous focal nonamyloid deposits, rare amyloid plaques). The course of Val/Val patients younger than age 55 was particularly long (19.9 +/- 7 months), and the isocortex bore the brunt of the pathology, suggesting a distinct variety. Conclusions: Polymorphism at codon 129 modulates the phenotype of sporadic Creutzfeldt-Jakob disease. The Val genotype enhances the production of proteinase-resistant PrP, and the Met/Val genotype facilitates its aggregation into amyloid plaques.