Isaacs A M, Powell C, Webb T E, Linehan J M, Collinge J, Brandner S
MRC Prion Unit, UCL Institute of Neurology, London, U.K.
Neuropathol Appl Neurobiol. 2008 Aug;34(4):446-56. doi: 10.1111/j.1365-2990.2008.00963.x.
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.
TDP-43, ubiquitin and PrP were analysed by immunohistochemistry and double-labelling immunofluorescence, in sporadic, acquired and inherited forms of human prion disease.
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.
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.
TAR-DNA结合蛋白43（TDP-43）是泛素阳性、tau蛋白阴性包涵体的额颞叶痴呆及运动神经元病中聚集物的主要泛素化蛋白。在阿尔茨海默病、路易体病及关岛帕金森痴呆综合征中也发现了异常的TDP-43免疫反应性。因此，我们旨在确定人类朊病毒病中是否存在TDP-43病理改变，其特征是脑内朊病毒蛋白（PrP）聚集体以淀粉样斑块或更弥散沉积物的形式存在。
采用免疫组化和双标免疫荧光法对散发性、获得性和遗传性人类朊病毒病中的TDP-43、泛素和PrP进行分析。
大多数PrP斑块含有泛素，而突触PrP沉积物与泛素无关。在任何类型的朊病毒病病例中均未发现异常的TDP-43包涵体，且TDP-43不与泛素阳性的PrP斑块或弥散性PrP聚集体共定位。
这些数据不支持TDP-43在朊病毒病发病机制中的作用，并表明TDP-43包涵体定义了一组独特的神经退行性疾病。
