Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; Department of Neurology, JA Toride Medical Center, Toride, Ibaraki, Japan.
J Neurol Sci. 2013 Dec 15;335(1-2):89-95. doi: 10.1016/j.jns.2013.08.035. Epub 2013 Sep 4.
We investigated the pathological features of frontotemporal lobar degeneration (FTLD) with fused in sarcoma protein (FUS) accumulation (FTLD-FUS) in the Japanese population. Only one out of nine FTLD-FUS cases showed pathology that corresponds to atypical FTLD with ubiquitin-positive inclusions (aFTLD-U). Five were basophilic inclusion body disease (BIBD) and two were neuronal intermediate filament inclusion disease. The last case was unclassifiable and was associated with dystrophic neurites (DNs) as the predominant FUS pathology. The results of this study indicate an ethnic difference from western countries. In Japan, BIBD is the most common subtype of FTLD-FUS and aFTLD-U is rare, a finding which contrasts with aFTLD-U being the most common form in western countries. Immunohistochemical analyses of these FTLD-FUS cases reveal that FUS abnormally accumulated in neuronal cytoplasmic inclusions (NCIs) and DNs has an immunohistochemical profile distinct from that of normal, nuclear FUS. NCIs and DNs are more readily stained than the nuclei by antibodies to the middle portion of FUS. Antibodies to the carboxyl terminal portion, on the other hand, stain the nuclei more readily than NCIs and DNs. Such an immunohistochemical profile of NCIs and DNs was similar to that of cytoplasmic granular FUS staining which we previously reported to be associated with dendrites and synapses. Redistribution of FUS from the nucleus to the cytoplasm could be associated with the formation of abnormal FUS aggregates in FTLD-FUS.
我们研究了日本人群中融合肉瘤蛋白（FUS）蓄积的额颞叶变性（FTLD-FUS）的病理特征。在 9 例 FTLD-FUS 病例中，只有 1 例表现出与泛素阳性包涵体（aFTLD-U）对应的非典型 FTLD 病理。5 例为嗜碱性包涵体病（BIBD），2 例为神经元中间丝包涵体病。最后一例无法分类，与以变性神经突起（DN）为主的 FUS 病理学相关。本研究结果表明与西方国家存在种族差异。在日本，BIBD 是最常见的 FTLD-FUS 亚型，aFTLD-U 很少见，这与西方国家 aFTLD-U 最常见的形式形成对比。对这些 FTLD-FUS 病例进行免疫组织化学分析表明，FUS 在神经元细胞质包涵体（NCIs）和 DNs 中异常蓄积，其免疫组织化学特征与正常核 FUS 不同。与 NCIs 和 DNs 相比，针对 FUS 中部的抗体更容易染色细胞核。另一方面，针对羧基末端的抗体更容易染色细胞核而不是 NCIs 和 DNs。NCIs 和 DNs 的这种免疫组织化学特征类似于我们之前报道的与树突和突触相关的细胞质颗粒状 FUS 染色。FUS 从细胞核重新分布到细胞质可能与 FTLD-FUS 中异常 FUS 聚集体的形成有关。
