Lack of TAR-DNA binding protein-43 (TDP-43) pathology in human prion diseases
Lack of TAR-DNA binding protein-43 (TDP-43) pathology in human prion diseases
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DOI：
10.1111/j.1365-2990.2008.00963.x
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发表时间：
2008-08-01
影响因子：
5
通讯作者：
Brandner, S.
中科院分区：
文献类型：
--
作者：
Isaacs, A. M.;Powell, C.;Brandner, S.
目的：TAR-DNA结合蛋白-43（TDP-43）是额颞叶痴呆伴泛素阳性、tau蛋白阴性包涵体和运动神经元病的聚集体中主要的泛素化蛋白。异常TDP-43免疫反应性也已在阿尔茨海默病、路易体病和关岛帕金森病-痴呆综合征中描述。因此，我们的目的是确定是否有TDP-43病理在人类朊病毒疾病，其特征是可变沉积的朊病毒蛋白（PrP）聚集在大脑中的淀粉样蛋白斑块或更弥漫的存款。材料和方法：TDP-43，泛素和PrP进行了分析，通过免疫组织化学和双标记免疫荧光，在散发性，获得性和遗传性形式的人类朊病毒病。结果：大多数PrP斑块含有泛素，而突触PrP沉积与泛素无关。在任何类型的朊病毒病病例中均未发现异常TDP-43包涵体，TDP-43未与泛素阳性PrP斑块或弥漫性PrP聚集体共定位。结论：这些数据不支持TDP-43在朊病毒疾病发病机制中的作用，并认为TDP-43包涵体定义了一组不同的神经退行性疾病。
Aims: TAR-DNA binding protein-43 (TDP-43) is the major ubiquitinated protein in the aggregates in frontotemporal dementia with ubiquitin-positive, tau-negative inclusions and motor neurone disease. Abnormal TDP-43 immunoreactivity has also been described in Alzheimer's disease, Lewy body diseases and Guam parkinsonism-dementia complex. We therefore aimed to determine whether there is TDP-43 pathology in human prion diseases, which are characterised by variable deposition of prion protein (PrP) aggregates in the brain as amyloid plaques or more diffuse deposits. Material and methods: TDP-43, ubiquitin and PrP were analysed by immunohistochemistry and double-labelling immunofluorescence, in sporadic, acquired and inherited forms of human prion disease. Results: Most PrP plaques contained ubiquitin, while synaptic PrP deposits were not associated with ubiquitin. No abnormal TDP-43 inclusions were identified in any type of prion disease case, and TDP-43 did not co-localize with ubiquitin-positive PrP plaques or with diffuse PrP aggregates. Conclusions: These data do not support a role for TDP-43 in prion disease pathogenesis and argue that TDP-43 inclusions define a distinct group of neurodegenerative disorders.