Numerous FUS-positive inclusions in an elderly woman with motor neuron disease
Numerous FUS-positive inclusions in an elderly woman with motor neuron disease
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DOI：
10.1111/j.1440-1789.2010.01146.x
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发表时间：
2011-04-01
期刊：
影响因子：
2.3
通讯作者：
Okamoto, Koichi
中科院分区：
文献类型：
--
作者：
Fujita, Yukio;Fujita, Sayaka;Okamoto, Koichi
我们报告一个75岁的日本女性运动神经元疾病（MND）的尸检病例，显示大量的神经元和神经胶质包涵体与抗融合肉瘤（FUS）抗体免疫染色。73岁时，她被诊断为MND，2年后死于呼吸功能不全。FUS基因的所有外显子均未发现突变。神经病理学检查显示前角细胞数量减少和锥体束变性。未观察到Bunina小体和43 kD泛素/磷酸化TAR DNA结合蛋白（pTDP-43）阳性的包涵体，如绞状或圆形包涵体。然而，嗜碱性包涵体（BI）经常观察到的前角，面神经核，舌下神经核，前庭神经核，齿状核和下橄榄核的其余神经元。在免疫组织化学分析中，BI显示出与抗FUS和抗泛素结合蛋白p62（p62）抗体的强免疫反应性。FUS阳性包涵体在部分神经元中保留核染色，少数神经胶质细胞中可见FUS阳性包涵体，在部分解剖区域FUS阳性包涵体多于p62阳性包涵体，在部分神经元中仅在部分BI中可见p62免疫反应。这些结果表明，BI的形成和TDP-43聚集有不同的致病机制，FUS可能在BI合并MND的发病机制中起重要作用。该患者报告的MND伴BI的发病年龄最大，在该患者中观察到的临床特征与经典散发性MND的临床特征无法区分。因此，我们认为FUS相关疾病的发病年龄和临床特征可能存在差异。
We report an autopsy case of a 75-year-old Japanese woman with motor neuron disease (MND) showing numerous neuronal and glial inclusions immunostained with anti-fused in sarcoma (FUS) antibody. At 73 years, she received a diagnosis of MND and died of respiratory insufficiency 2 years later. No mutation was found in all exons of the FUS gene. Neuropathological examination revealed a reduced number of anterior horn cells and degeneration of the pyramidal tracts. Neither Bunina bodies nor inclusions positive for ubiquitin/phosphorylated TAR DNA binding protein of 43 kD (pTDP-43), such as skein-like or round inclusions, were observed. However, basophilic inclusions (BIs) were frequently observed in the remaining neurons of the anterior horns, facial nuclei, hypoglossal nuclei, vestibular nuclei, dentate nuclei and inferior olivary nuclei. In an immunohistochemical analysis, the BIs showed strong immunoreactivity with anti-FUS and anti-ubiquitin-binding protein p62 (p62) antibodies. The nuclear staining of FUS was preserved in some neurons with FUS-positive inclusions, and a few FUS-positive glial inclusions were found. FUS-positive inclusions were more common than p62-positive inclusions in some anatomical regions, and in some neurons, p62 immunoreactivity was observed in only parts of the BIs. These results suggest that BI formation and TDP-43 aggregation have different pathogenic mechanisms, and FUS may play an important role in the pathogenesis of MND with BIs. This patient has the oldest reported age of onset for MND with BIs, and clinical features observed in this patient were indistinguishable from those of classic sporadic MND. Therefore, we consider that the age of onset and clinical features of FUS-related disorders may be variable.