TDP-43-immunoreactive neuronal and glial inclusions in the neostriatum in amyotrophic lateral sclerosis with and without dementia
TDP-43-immunoreactive neuronal and glial inclusions in the neostriatum in amyotrophic lateral sclerosis with and without dementia
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DOI：
10.1007/s00401-007-0285-7
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发表时间：
2007-09
影响因子：
12.7
通讯作者：
Hai-xin Zhang;C. Tan;F. Mori;K. Tanji;A. Kakita;H. Takahashi;K. Wakabayashi
中科院分区：
文献类型：
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作者：
Hai-xin Zhang;C. Tan;F. Mori;K. Tanji;A. Kakita;H. Takahashi;K. Wakabayashi
TDP-43是肌萎缩侧索硬化症（ALS）和额颞叶变性中泛素阳性、tau阴性包涵体的主要成分。我们对14例典型ALS（cALS）、6例ALS伴痴呆（ALS-D）和20例对照组的新纹状体进行了化学检测。在20例ALS患者中，19例的新纹状体小神经元内发现TDP-43阳性的新月形或圆形包涵体，而对照组中未发现。在大神经元中发现两种类型的包涵体：泛素阳性，TDP-43阴性的杆状包涵体和泛素和TDP-43阳性的多形性包涵体。后者是ALS特有的;在7例cALS和所有ALS-D中发现了它们。12例cALS和所有ALS-D中均可见TDP-43阳性胶质包涵体。这些TDP-43阳性神经元和神经胶质包涵体在ALS-D中比cALS中更多。在ALS-D中，所有病例均发现黑质神经元丢失，而仅2例在新纹中发现轻度胶质增生，但无明显神经元丢失。这些发现表明，新纹状体也参与了ALS伴痴呆和不伴痴呆的疾病过程。
TDP-43 is a major component of ubiquitin-positive, tau-negative inclusions in amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration. We immunohistochemically examined the neostriatum from 14 cases of classic ALS (cALS), six cases of ALS with dementia (ALS-D), and 20 control subjects. TDP-43-positive, crescent or circular inclusions were found in neostriatal small neurons in 19 of 20 cases of ALS, but not in controls. Two types of inclusions were found in the large neurons: ubiquitin-positive, TDP-43-negative rod-like inclusions, and ubiquitin- and TDP-43-positive pleomorphic inclusions. The latter were specific to ALS; they were found in seven cases of cALS and in all of ALS-D. TDP-43-positive glial inclusions were also found in 12 cases of cALS and in all of ALS-D. These TDP-43-positive neuronal and glial inclusions were more numerous in ALS-D than cALS. In ALS-D, neuronal loss in the substantia nigra was found in all the cases, whereas mild gliosis without obvious neuronal loss was noted in the neostriaum in only two cases. These findings suggest that the neostriatum is also involved in the disease process of ALS with and without dementia.