Neuronal intermediate filament inclusion disease may be incorrectly classified as a subtype of FTLD-FUS.
Neuronal intermediate filament inclusion disease may be incorrectly classified as a subtype of FTLD-FUS.
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DOI：
10.17879/freeneuropathology-2020-2639
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发表时间：
2020-01-01
影响因子：
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通讯作者：
Dickson, Dennis W
中科院分区：
文献类型：
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作者：
Bieniek, Kevin F;Josephs, Keith A;Dickson, Dennis W
背景：大多数额颞叶变性（FTLD）病例的特征是局灶性皮质萎缩，伴有潜在的tau或TDP-43蛋白病变。然而，一部分FTLD病例缺乏tau和TDP-43的免疫反应性，但具有泛素阳性的神经元包涵体，称为非典型FTLD （aFTLD-U）。研究表明，aFTLD-U中的泛素阳性包涵体对融合肉瘤（FUS）具有免疫反应性。因此，目前该疾病的病种是FTLD-FUS，被认为不仅包括afld - u，还包括神经元中间丝包涵体病（NIFID）和亲碱性包涵体病。目的：比较aFTLD-U与NIFID病例的病理特征。方法：我们回顾了15例患者的神经病理学（男性10例，女性5例；死亡时平均年龄54岁（41-69岁）），死前临床诊断为额颞叶痴呆，病理诊断为aFTLD-U （n=8）或NIFID （n=7）。切片用FUS、TDP-43和α -间连蛋白（alphaINX）抗体进行免疫组织化学和免疫电镜处理。结果：8例患者病理特征符合FTLD-FUS，伴严重纹状体萎缩（7/8），核内包涵体和蚓状包涵体呈fus阳性，但无alphaINX免疫反应。5例具有与NIFID一致的特征，FUS和alphaINX均呈神经元包涵体阳性。只有2例NIFID患者出现纹状体萎缩。2例患者有与NIFID一致的alphainx阳性神经元包涵体，但均缺乏纹状体萎缩和FUS免疫反应性。令人惊讶的是，这两个NIFID病例中有一个病变对TDP-43免疫反应。讨论：虽然FUS病理仍然是aFTLD-U的一个突出特征，但存在病理异质性，包括罕见的nifd病例伴TDP-43-而非FUS阳性包涵体。
BACKGROUND: The majority of cases of frontotemporal lobar degeneration (FTLD) are characterized by focal cortical atrophy with an underlying tau or TDP-43 proteinopathy. A subset of FTLD cases, however, lack tau and TDP-43 immuno-reactivity, but have neuronal inclusions positive for ubiquitin, referred to as atypical FTLD (aFTLD-U). Studies have demonstrated that ubiquitin-positive inclusions in aFTLD-U are immuno-reactive for fused in sarcoma (FUS). As such, the current nosology for this entity is FTLD-FUS, which is thought to include not only aFTLD-U, but also neuronal intermediate filament inclusion disease (NIFID) and basophilic inclusion body disease.OBJECTIVE: To compare pathological features of cases of aFTLD-U and NIFID.METHODS: We reviewed the neuropathology of 15 patients (10 males and 5 females; average age at death 54 years (range 41-69 years)) with an antemortem clinical diagnosis of a frontotemporal dementia and pathological diagnosis of aFTLD-U (n=8) or NIFID (n=7). Sections were processed for immunohistochemistry and immunoelectron microscopy with FUS, TDP-43, and alpha-internexin (alphaINX) antibodies.RESULTS: Eight cases had pathologic features consistent with FTLD-FUS, with severe striatal atrophy (7/8 cases), as well as FUS-positive neuronal cytoplasmic and vermiform intranuclear inclusions, but no alphaINX immuno-reactivity. Five cases had features consistent with NIFID, with neuronal inclusions positive for both FUS and alphaINX. Striatal atrophy was present in only 2 of the NIFID cases. Two cases had alphaINX-positive neuronal inclusions consistent with NIFID, but both lacked striatal atrophy and FUS immunoreactivity. Surprisingly, one of these two NIFID cases had lesions immunoreactive for TDP-43.DISCUSSION: While FUS pathology remains a prominent feature of aFTLD-U, there is pathologic heterogeneity, including rare cases of NIFID with TDP-43- rather than FUS-positive inclusions.