Neuroanatomic Profile of Polyglutamine Immunoreactivity in Huntington Disease Brains
Neuroanatomic Profile of Polyglutamine Immunoreactivity in Huntington Disease Brains
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DOI：
10.1097/nen.0b013e318198d320
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发表时间：
2009-03-01
影响因子：
3.2
通讯作者：
White, Charles L., III
中科院分区：
文献类型：
--
作者：
Herndon, Emily S.;Hladik, Christa L.;White, Charles L., III
亨廷顿病（HD）的病理学标志是存在含有多聚谷氨酰胺的亨廷顿蛋白片段的神经元内聚集体。单克隆抗体IC2是一种针对正常人TATA结合蛋白的商业抗体，可检测谷氨酰胺残基的长片段。使用IC2作为突变亨廷顿蛋白的替代标记物，我们免疫染色19例HD，10例正常对照，和10例额颞叶变性与泛素化包涵体作为疾病对照。在HD患者中，新皮质、纹状体、海马、外侧膝状体、脑桥基底部有一致的IC 2免疫反应阳性。延髓网状结构和小脑齿状核。正常和患病对照组仅在黑质、蓝斑和垂体中显示IC2免疫反应性。5例HD病例和5例正常对照的染色显示不太一致和诊断有用的形态学免疫反应性。这些结果表明，广泛的IC2免疫反应性是存在于不同的中枢神经系统领域的HD，并在适当的设置，IC2染色可以是一个有用的工具，在HD的尸检诊断时，神经黑色素，神经元群体是避免的。
A pathologic hallmark of Huntington disease (HD) is the presence of intraneuronal aggregates of polyglutamine-containing huntingtin protein fragments. Monoclonal antibody IC2 is a commercial antibody to normal human TATA-binding protein that detects long stretches of glutamine residues. Using IC2 as a surrogate marker for mutant huntingtin protein, we immunostained 19 HD cases, 10 normal controls, and 10 cases of frontotemporal degeneration with ubiquitinated inclusions as diseased controls. In the HD cases, there was consistent IC2 immunoreactivity in the neocortex, striatum, hippocampus, lateral geniculate body, basis pontis. medullary reticular formation, and cerebellar dentate nucleus. The normal and diseased controls demonstrated IC2 immunoreactivity only in the substantia nigra, locus coeruleus, and pituitary gland. Staining of 5 HD cases and 5 normal controls revealed a less consistent and less diagnostically useful morphologic immunoreactivity profile. These results indicate that widespread IC2 immunoreactivity is present in diverse central nervous system areas in HD, and that in the appropriate setting, IC2 staining can be a useful tool in the postmortem diagnosis of HD when neuromelanin-containing, neuronal populations are avoided.