Neuropathological studies on Parkinson's disease and amyotrophic lateral sclerosis

我们研究了帕金森病（PD）的高尔基体（GA）是否在黑质神经元中断裂。我们用抗tgn46抗体免疫细胞化学方法在对照病例中未观察到片段化的GA。在PD中，无包涵体的神经元中有3%的GA断裂，有路易小体的神经元中有5%的GA断裂。相比之下，在含有苍白体的19%的神经元中发现了碎片化的GA。由于苍白体代表脑干路易体发育的早期阶段，我们的研究结果表明，在路易体形成过程中，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传递中起着重要作用。我们证明了在ALS病例中，转铁蛋白定位于布尼纳体和一些嗜碱性包涵体。而束状夹杂物、路易体样夹杂物或圆形夹杂物未表现出明显的转铁蛋白免疫反应。最近，TDP-43被认为是ALS和额颞叶变性下运动神经元中泛素化神经元胞质内含物的主要成分。几乎所有TDP-43免疫反应异常的前角细胞均出现GA断裂。这些结果表明，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的功能障碍有关。

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.