Department of Pathology, Center for Bioresources, Brain Research Institute, University of Niigata, Niigata, Japan.
Neuropathol Appl Neurobiol. 2012 Feb;38(1):54-60. doi: 10.1111/j.1365-2990.2011.01175.x.
Phosphorylated TDP-43 (pTDP-43) is the pathological protein responsible for amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. Recently, it has been reported that accumulation of pTDP-43 can occur in the brains of patients with argyrophilic grain disease (AGD), in which phosphorylated 4-repeat tau is the pathological protein. To elucidate the association of ALS with AGD, we examined the brains from 37 consecutively autopsied patients with sporadic ALS (age range 45-84 years, mean 71.5 ± 9.0 years).
Sections from the frontotemporal lobe were stained with the Gallyas-Braak method and also immunostained with antibodies against phosphorylated tau, 4-repeat tau and pTDP-43.
Fourteen (38%) of the 37 ALS patients were found to have AGD. With regard to staging, 5 of these 14 cases were rated as I, 4 as II and 5 as III. pTDP-43 immunohistochemistry revealed the presence of positive neuronal and glial cytoplasmic inclusions in the affected medial temporal lobe in many cases (93% and 64%, respectively). On the other hand, pTDP-43-positive small structures corresponding to argyrophilic grains were observed only in one case. A significant correlation was found between AGD and the Braak stage for neurofibrillary pathology (stage range 0-V, mean 2.1). However, there were no significant correlations between AGD and any other clinicopathological features, including dementia.
The present findings suggest that co-occurrence of AGD in ALS is not uncommon, and in fact comparable with that in a number of diseases belonging to the tauopathies or α-synucleinopathies.
磷酸化 TDP-43（pTDP-43）是导致肌萎缩侧索硬化症（ALS）的病理性蛋白，ALS 是一种致命的神经退行性疾病。最近有报道称，在颗粒性苍白球病（AGD）患者的大脑中也会出现 pTDP-43 的积累，而磷酸化 4 重复 tau 是其病理性蛋白。为了阐明 ALS 与 AGD 的关联，我们检查了 37 例连续尸检的散发性 ALS 患者（年龄 45-84 岁，平均 71.5±9.0 岁）的大脑。
使用 Gallyas-Braak 方法对额颞叶切片进行染色，并使用针对磷酸化 tau、4 重复 tau 和 pTDP-43 的抗体进行免疫染色。
在 37 例 ALS 患者中，有 14 例（38%）被发现患有 AGD。在分期方面，这 14 例中有 5 例为 I 期，4 例为 II 期，5 例为 III 期。pTDP-43 免疫组化显示，受影响的内侧颞叶中存在大量阳性神经元和神经胶质细胞质包涵体（分别为 93%和 64%）。另一方面，仅在 1 例中观察到与颗粒性苍白球对应的 pTDP-43 阳性小结构。AGD 与神经纤维病理的 Braak 分期之间存在显著相关性（分期范围 0-V，平均 2.1）。然而，AGD 与包括痴呆在内的任何其他临床病理特征之间均无显著相关性。
本研究结果表明，AGD 在 ALS 中的共存并不罕见，实际上与许多属于 tau 病或α-突触核蛋白病的疾病相当。
