Department of Neurology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
J Neuropathol Exp Neurol. 2012 Jul;71(7):625-30. doi: 10.1097/NEN.0b013e31825b9680.
α-Synuclein pathology was examined in the brains and spinal cords of 10 patients with amyotrophic lateral sclerosis (ALS)/parkinsonism-dementia complex (PDC) in the Kii Peninsula, Japan. Various types of phosphorylated α-synuclein-positive structures including neuronal cytoplasmic inclusions, dystrophic neurites, and glial cytoplasmic inclusions were found in all ALS/PDC cases. There were phosphorylated α-synuclein-positive neurons in 8 cases (80%), and the amygdala was most severely affected. Phosphorylated α-synuclein was distributed mainly in the limbic system and brainstem; tau pathology was more prevalent than α-synuclein pathology in most affected areas. In the substantia nigra, periaqueductal gray, locus coeruleus, raphe nuclei, dorsal nucleus of the vagus nerve, hypoglossal nucleus or ventral horn, and intermediolateral nucleus of the spinal cord, α-synuclein pathology was more predominant than tau pathology in only 1 or 2 patients. Phosphorylated α-synuclein- positive structures were not found in the molecular layer of the cerebellum. Phosphorylated α-synuclein frequently colocalized with tau in neuron cell bodies, neurites, and glia. Immunoblots of sarkosyl-insoluble fractions extracted from the brain of 1 patient showed a triplet of α-synuclein-immunoreactive bands that were ubiquitinated. These results suggest that interaction between tau and α-synuclein be involved in the pathogenesis of Kii ALS/PDC.
在日本纪伊半岛的 10 名肌萎缩侧索硬化症（ALS）/帕金森病痴呆综合征（PDC）患者的大脑和脊髓中检查了α-突触核蛋白病理学。在所有 ALS/PDC 病例中均发现了各种类型的磷酸化α-突触核蛋白阳性结构，包括神经元细胞质内含物、营养不良神经突和神经胶质细胞质内含物。在 8 例（80%）中存在磷酸化α-突触核蛋白阳性神经元，且杏仁核受影响最严重。磷酸化α-突触核蛋白主要分布在边缘系统和脑干中；在大多数受影响的区域中，tau 病理学比α-突触核蛋白病理学更为普遍。在黑质、导水管周围灰质、蓝斑、中缝核、迷走神经背核、舌下核或腹角以及脊髓中间外侧核中，只有 1 或 2 例患者中α-突触核蛋白病理学比 tau 病理学更为突出。小脑分子层中未发现磷酸化α-突触核蛋白阳性结构。磷酸化α-突触核蛋白在神经元胞体、神经突和神经胶质中经常与 tau 共定位。从 1 例患者大脑中提取的 Sarkosyl 不溶性级分的免疫印迹显示出三链α-突触核蛋白免疫反应性带，这些带被泛素化。这些结果表明 tau 和α-突触核蛋白之间的相互作用可能参与了纪伊 ALS/PDC 的发病机制。
