Unique tauopathy in Fukuyama-type congenital muscular dystrophy
Unique tauopathy in Fukuyama-type congenital muscular dystrophy
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DOI：
10.1097/01.jnen.0000190069.10633.c2
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发表时间：
2005-12-01
影响因子：
3.2
通讯作者：
Murayama, S
中科院分区：
文献类型：
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作者：
Saito, Y;Motoyoshi, Y;Murayama, S
福山型先天性肌营养不良症（FCMD）是一种以肌营养不良和大脑、小脑皮质发育不全为特征的疾病。我们研究了7例胎儿后（14-34岁）和2例胎儿（18和20周胎龄）FCMD病例大脑中tau蛋白病变的程度和性质。在所有胎后病例中，除了可预测的部位（如海马）外，在大脑皮质发育不全的区域也发现了tau蛋白病。在胎儿病例中，畸形大脑皮质的神经元被抗异常磷酸化tau抗体弥漫性免疫染色。通过免疫电子显微镜，抗体的表位与微管样束内的细胞过程中突出通过破坏胶质细胞界膜。在Western印迹分析中，在胎儿和胎儿后的情况下，检测到一个独特的50 kDa的tau带。此外，在后者中还检测到3至4条60至68 kD的tau带，类似于阿尔茨海默病中的tau。去磷酸化后，胎儿和胎儿后病例的不溶性tau蛋白显示出高度相似的免疫印迹模式。tau蛋白的异常磷酸化可能与FCMD中皮质发育不良的发生有关，并可能揭示tau蛋白在中枢神经系统发育中的生物学功能。
Fukuyama-type congenital muscular dystrophy (FCMD) is characterized by muscular dystrophy and cortical dysgenesis of the cerebrum and cerebellum. We investigated the extent and nature of tauopathy in the brains of 7 postfetal (14-34 years of age) and 2 fetal (18- and 20-week gestational age) FCMD cases. In all postfetal cases, tauopathy was found in the areas of cortical dysgenesis in the cerebrum, in addition to predictable sites such as the hippocampus. In fetal cases, the neuropil of malformed cerebral cortex was diffusely immumostained with anti-aberrantly phosphorylated tau antibodies. By immunoelectron microscopy, the epitope of the antibodies was associated with microtubule-like bundles within cellular processes protruding through disrupted glia limitans. In Western blot analysis, a unique 50-kDa band of tau was detected in a fetal and a postfetal case. In addition, 3 to 4 tau bands of 60 to 68 kD, similar to tau in Alzheimer disease, were also detected in the latter. After dephosphorylation, the insoluble tau from the fetal and the postfetal cases showed highly similar immunoblotting patterns. This anomalous phosphorylation of tau may be related to the development of the cortical dysgenesis in FCMD and may shed light on the biologic function of tau in the development of the central nervous system.