Coexistence of Huntington's disease and amyotrophic lateral sclerosis: a clinicopathologic study.
Coexistence of Huntington's disease and amyotrophic lateral sclerosis: a clinicopathologic study.
复制标题
DOI：
10.1007/s00401-012-1005-5
复制
发表时间：
2012-11
影响因子：
12.7
通讯作者：
Paulson HL
中科院分区：
文献类型：
--
作者：
Tada M;Coon EA;Osmand AP;Kirby PA;Martin W;Wieler M;Shiga A;Shirasaki H;Tada M;Makifuchi T;Yamada M;Kakita A;Nishizawa M;Takahashi H;Paulson HL
我们报告了四名经基因证实的亨廷顿病(HD)和散发性肌萎缩侧索硬化症(ALS)患者的回顾性病例系列，其中两例检查了大脑和脊髓。神经病理学评估包括聚谷氨酰胺补充法检测活性聚谷氨酰胺聚集部位，以及TDP-43病理的生化和免疫组织化学评估。先天性肌萎缩侧索硬化症和肌萎缩侧索硬化症的临床顺序各不相同，所有病例的肌萎缩侧索硬化症都发生在55岁中期以后。HD和ALS的神经病理特征在两例中同时存在：新纹状体和上下运动神经元中有神经元丢失和胶质增生，剩余的下运动神经元中有布尼娜小体和泛素免疫反应的skein样包涵体。1例为早期HD病理，1例为晚期HD。扩张的聚谷氨酰胺免疫反应包涵体和TDP-43免疫反应包涵体广泛存在于中枢神经系统的许多区域，包括运动皮质和脊髓前角。虽然这两种不同的包涵体共存于少数神经元中，但这两种蛋白并不共定位于包涵体内。TDP-43免疫反应阳性包涵体在大脑皮层的区域分布与扩张的聚谷氨酰胺免疫反应包涵体有些相似。在1例TDP-43免疫印迹检查中，发现与ALS相似的TDP-43亚型。我们的发现表明，一组罕见的老年HD患者容易发展为ALS的特征，其非典型的TDP-43分布类似于聚集的突变亨廷顿蛋白。突变型多谷氨酰胺蛋白表达引起的年龄依赖性神经元功能障碍可能与一小部分HD患者的TDP-43相关运动神经元病的晚年发展有关。
We report a retrospective case series of four patients with genetically confirmed Huntington’s disease (HD) and sporadic amyotrophic lateral sclerosis (ALS), examining the brain and spinal cord in two cases. Neuropathological assessment included a polyglutamine recruitment method to detect sites of active polyglutamine aggregation, and biochemical and immunohistochemical assessment of TDP-43 pathology. The clinical sequence of HD and ALS varied, with the onset of ALS occurring after the mid-fifties in all cases. Neuropathologic features of HD and ALS coexisted in both cases examined pathologically: neuronal loss and gliosis in the neostriatum and upper and lower motor neurons, with Bunina bodies and ubiquitin-immunoreactive skein-like inclusions in remaining lower motor neurons. One case showed relatively early HD pathology while the other was advanced. Expanded polyglutamine-immunoreactive inclusions and TDP-43-immunoreactive inclusions were widespread in many regions of the CNS, including the motor cortex and spinal anterior horn. Although these two different inclusions coexist in a small number of neurons, the two proteins did not co-localize within inclusions. The regional distribution of TDP-43-immunoreactive inclusions in the cerebral cortex was somewhat similar to that of expanded polyglutamine-immunoreactive inclusions. In the one case examined by TDP-43 immunoblotting, similar TDP-43 isoforms were observed as in ALS. Our findings suggest the possibility that a rare subset of older HD patients is prone to develop features of ALS with an atypical TDP-43 distribution that resembles that of aggregated mutant huntingtin. Age-dependent neuronal dysfunction induced by mutant polyglutamine protein expression may contribute to later-life development of TDP-43 associated motor neuron disease in a small subset of patients with HD.
登录
查看更多内容
影响因子：
--
作者：
Geser, Felix;Martinez-Lage, Maria;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
DOI：
10.1097/nen.0b013e318198d320
发表时间：
2009-03-01
影响因子：
3.2
作者：
Herndon, Emily S.;Hladik, Christa L.;White, Charles L., III
通讯作者：
White, Charles L., III
影响因子：
8.6
作者：
Kanai, Kazuaki;Kuwabara, Satoshi;Hattori, Takamichi
通讯作者：
Hattori, Takamichi
影响因子：
9.9
作者：
Lee, T.;Li, Y. R.;Gitler, A. D.
通讯作者：
Gitler, A. D.
影响因子：
5.7
作者：
Da Cruz S;Cleveland DW
通讯作者：
Cleveland DW