Piao Yue-Shan, Hayashi Shintaro, Wakabayashi Koichi, Kakita Akiyoshi, Aida Izumi, Yamada Mitsunori, Takahashi Hitoshi
Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata 951-8585, Japan.
Acta Neuropathol. 2002 May;103(5):469-74. doi: 10.1007/s00401-001-0488-2. Epub 2002 Jan 25.
Immunohistochemical localization of tau in the cerebellar cortex was carried out using a mouse monoclonal antibody against phosphorylation-dependent tau (AT8) in brain tissue (cerebellum) from 13 patients with progressive supranuclear palsy (PSP), 7 patients with corticobasal degeneration (CBD) and 5 age-matched control subjects. Purkinje cell somata that showed diffuse granular accumulation of cytoplasmic tau were found occasionally in 9 of the 13 patients with PSP (69%) and in 4 of the 7 patients with CBD (57%). Tau-positive doughnut-shaped structures were also found occasionally in the cerebellar molecular layer in 6 of the 13 patients with PSP (46%) and 2 of the 7 patients with CBD (29%). No tau immunoreactivity was detected in the cerebellar cortex in the control tissue. In the tissue from one patient with PSP, we also performed a double-labeling immunofluorescence study with anti-glial fibrillary acidic protein (GFAP) antibody and AT8, as well as an immuno-electron microscopic study with AT8. In tau-positive Purkinje cell somata and dendrites, the reaction product was localized mainly within the rough endoplasmic reticulum and free ribosomes. Tau-positive doughnut-shaped structures were located in the GFAP-positive radial processes of Bergmann's glia and were present in the outer areas of inclusions reminiscent of Lewy bodies, which consist of aggregated pathological tau filaments. In conclusion, we have demonstrated a novel tau pathology that affects Purkinje cells and Bergmann's glia in patients with PSP and CBD, indicating that the cerebellar cortex can be involved in the disease processes in PSP and CBD.
利用抗磷酸化依赖性tau蛋白的小鼠单克隆抗体（AT8），对13例进行性核上性麻痹（PSP）患者、7例皮质基底节变性（CBD）患者及5例年龄匹配的对照者的脑组织（小脑）进行tau蛋白在小脑皮质中的免疫组织化学定位。在13例PSP患者中的9例（69%）以及7例CBD患者中的4例（57%）偶尔发现浦肯野细胞胞体出现胞质tau蛋白的弥漫性颗粒状聚集。在13例PSP患者中的6例（46%）以及7例CBD患者中的2例（29%）的小脑分子层中也偶尔发现tau阳性的甜甜圈状结构。对照组织的小脑皮质未检测到tau免疫反应性。在1例PSP患者的组织中，我们还进行了抗胶质纤维酸性蛋白（GFAP）抗体与AT8的双标记免疫荧光研究，以及AT8的免疫电子显微镜研究。在tau阳性的浦肯野细胞胞体和树突中，反应产物主要定位于粗面内质网和游离核糖体中。tau阳性的甜甜圈状结构位于伯格曼胶质细胞的GFAP阳性放射状突起中，且存在于类似路易小体的包涵体的外部区域，路易小体由聚集的病理性tau细丝组成。总之，我们证实了一种新的tau病理改变，其影响PSP和CBD患者的浦肯野细胞和伯格曼胶质细胞，表明小脑皮质可能参与PSP和CBD的疾病进程。
