Neuropathological studies on Parkinson's disease and amyotrophic lateral sclerosis

我们研究了帕金森病（PD）黑质神经元中高尔基体（GA）是否断裂。我们没有观察到破碎的GA在黑质神经元的contoro情况下，通过免疫细胞化学与抗TGN 46抗体。在PD中，GA在3%的黑质神经元中不含内含物，在5%的具有Lewy小体的神经元中碎片化。与此相反，19%的神经元含有苍白体的碎片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，α-突触核蛋白阳性聚集体的细胞毒性在路易体形成的过程中降低。转铁蛋白是一种铁结合蛋白，在循环三价铁向组织的转运和递送中起重要作用。我们证明，转铁蛋白定位在布尼纳体和一些嗜碱性包涵体在ALS的情况下。而线状包涵体、Lewy小体状包涵体或圆形包涵体未见明显的转铁蛋白免疫反应。最近，TDP-43被鉴定为在ALS和额颞叶变性的下运动神经元中观察到的泛素化神经元胞质内含物的主要组分。几乎所有TDP-43免疫反应异常的前角细胞都显示GA碎裂。这些结果表明，异常TDP-43免疫反应的神经元与ALS运动神经元分泌途径的功能障碍。

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.