Miki Yasuo, Mori Fumiaki, Seino Yusuke, Tanji Kunikazu, Yoshizawa Tadashi, Kijima Hiroshi, Shoji Mikio, Wakabayashi Koichi
Department of Neuropathology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Neuropathology. 2018 Oct;38(5):521-528. doi: 10.1111/neup.12484. Epub 2018 Jun 25.
Sporadic amyotrophic lateral sclerosis (sALS) is characterized pathologically by loss of upper and lower motor neurons with occurrence of transactivation response DNA-binding protein 43 kDa (TDP-43)-immunoreactive skein-like and round hyaline inclusions. Lewy body-like hyaline inclusions (LBHIs) are also found in a small proportion of sALS cases as well as in individuals with familial ALS with mutations in the Cu/Zu superoxide dismutase (SOD1) gene. LBHIs in sALS are immunopositive for TDP-43, but not for SOD1. The occurrence of Bunina bodies (BBs) is another key pathological feature of sALS. BBs are immunonegative for TDP-43 but immunopositive for cystatin C, transferrin, peripherin and sortilin-related receptor CNS expressed 2 (SorCS2). Despite differences between BBs and TDP-43 inclusions in terms of protein constituents and ultrastructure, the two inclusions are known to be linked. We recently encountered a case of sALS of 10 months duration in which many round hyaline inclusions, LBHIs and BBs were found in the anterior horn cells of the spinal cord. Our immunohistochemical and ultrastructural examinations revealed the presence of BBs within the skein-like and round hyaline inclusions, and in the LBHIs. Colocalization of BB-related proteins (cystatin C, transferrin and SorCS2) and TDP-43 was also confirmed in the halo of LBHIs as well as in the marginal portion of the skein-like and round hyaline inclusions. These findings suggest that there is some relationship between BBs and TDP-43-immunoreactive inclusions in terms of their formation processes.
散发性肌萎缩侧索硬化症（sALS）的病理特征是上下运动神经元丧失，出现反式激活反应DNA结合蛋白43 kDa（TDP-43）免疫反应性的丝状和圆形透明包涵体。在一小部分sALS病例以及铜/锌超氧化物歧化酶（SOD1）基因突变的家族性ALS患者中也发现了路易体样透明包涵体（LBHIs）。sALS中的LBHIs对TDP-43免疫阳性，但对SOD1免疫阴性。布尼纳小体（BBs）的出现是sALS的另一个关键病理特征。BBs对TDP-43免疫阴性，但对胱抑素C、转铁蛋白、外周蛋白和sortilin相关受体中枢神经系统表达2（SorCS2）免疫阳性。尽管BBs和TDP-43包涵体在蛋白质成分和超微结构方面存在差异，但已知这两种包涵体是相关联的。我们最近遇到一例病程为10个月的sALS病例，在脊髓前角细胞中发现了许多圆形透明包涵体、LBHIs和BBs。我们的免疫组织化学和超微结构检查显示，在丝状和圆形透明包涵体以及LBHIs中存在BBs。在LBHIs的晕圈以及丝状和圆形透明包涵体的边缘部分也证实了BB相关蛋白（胱抑素C、转铁蛋白和SorCS2）与TDP-43的共定位。这些发现表明，BBs与TDP-43免疫反应性包涵体在形成过程方面存在某种关系。
