Neuropathological studies on Parkinson's disease and amyotrophic lateral sclerosis

我们观察了帕金森氏病(PD)患者黑质神经元中高尔基体(GA)是否碎裂。用抗TGN46抗体进行免疫细胞化学染色，未在对照组黑质神经元内观察到GA片段化。帕金森病组无包涵体的黑质神经元中有3%的神经元GA断裂，有路易小体的黑质神经元中有5%的GA断裂。相反，在含有苍白小体的神经元中，有19%的神经元出现GA片段化。由于苍白小体代表了脑干路易斯小体发育的早期阶段，我们的结果表明，在路易小体形成的过程中，α-突触核蛋白阳性聚集体的细胞毒性降低。转铁蛋白是一种铁结合蛋白，在循环铁向组织的运输和输送中起着重要作用。我们发现转铁蛋白定位于肌萎缩侧索硬化症患者的布尼娜小体和一些嗜碱性包涵体中。相反，丝蛋白样包涵体和路易体状包涵体或圆形包涵体未显示明显的转铁蛋白免疫反应活性。最近，TDP-43被认为是泛素化神经元胞浆内包涵体的主要成分，在ALS的下运动神经元和伴随泛素化包涵体的额颞叶变性中观察到。TDP-43免疫反应异常的前角细胞几乎全部呈现GA断裂。提示TDP-43免疫反应异常的神经元与肌萎缩侧索硬化症运动神经元分泌通路功能障碍有关。

We examined whether the Golgi apparatus (GA) is fragmented in nigral neurons in Parkinson's disease (PD). We did not observe fragmented GA in nigral neurons in contoro cases by immunocytochemistry with an anti-TGN46 antibody. In PD, the GA was fragmented in 3% of the nigral neurons without inclusions, and in 5% of the neurons with Lewy bodies. In contrast, fragmented GA was noted in 19% of the neurons containing pale bodies. Since pale bodies represent early stages in the development of brainstem Lewy bodies, our results suggest that the cytotoxicity of alpha-synuclein-positive aggregates is reduced in the process of Lewy body formation. Transferrin, an iron-binding protein, plays an important role in the transport and delivery of circulating ferric iron to the tissues. We demonstrated that transferrin localized in Bunina bodies and some of the basophilic inclusions in ALS cases. In contrast, skein-like inclusions and Lewy body-like inclusions or round inclusions did not show obviously detectable transferrin immunoreactivities. Recently, TDP-43 was identified as a major component of ubiquitinated neuronal cytoplasmic inclusions observed in lower motor neurons in ALS and frontotemporal lobar degeneration with ubiquitinated inclusions. Almost all of the anterior horn cells with abnormal TDP-43 immunoreactivities showed GA fragmentation. These results suggest that neurons with abnormal TDP-43 immunoreactivities are associated with dysfunction of the secretory pathway in motor neurons in ALS.