Furukawa Yoshiko, Iseki Eizo, Hino Hiroaki, Kanai Akiko, Odawara Toshinari, Kosaka Kenji
Department of Psychiatry, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan.
Neuropathology. 2004 Mar;24(1):38-45. doi: 10.1111/j.1440-1789.2003.00538.x.
Nine cases of atypical Pick's disease without Pick bodies were investigated immunohistochemically. Ubiquitin (ub)-positive and tau-negative structures were mainly found in the cerebral cortex and hippocampal dentate gyrus. In the cerebral cortex, most of the ub-positive structures had ub-positive dendrites in the neuropil, although some also showed diffuse ub-positive staining in the neuronal cytoplasm. These ub-positive structures were distributed throughout layers II-IIIab and layers V-VI. Granular cells of the dentate gyrus had ub-positive intraneuronal inclusions. When the numbers of ub-positive neurons and dendrites were evaluated in relation to the degree of neuronal loss in the cerebral cortex, the number of ub-positive neurons was significantly lower in regions showing very mild neuronal loss and higher in regions showing moderate neuronal loss. In contrast, ub-positive dendrites were detected even in cortical regions showing very mild neuronal loss. Immunoelectron-microscopically, ub-positive structures contained ub-positive ribosome-like granular components in the neuronal cytoplasm and dendrites, which were occasionally related to the rough endoplasmic reticulum and accompanied by a few filamentous components. Almost all ub-positive structures were positive for ub-binding protein p62 in double-immunostaining method. Some ub-positive or negative neurons in the cerebral cortex were positively immunolabeled with anti-ub ligase (Parkin) and anti-ub C-terminal hydrolase antibodies, whereas dendrites were not labeled by these antibodies. From the present study, it is suggested that in the cerebral cortex, these ubiquitinated proteins may firstly accumulate in the dendrites at the onset of neuronal degeneration, then appear in the neuronal cytoplasm before finally disappearing with neuronal loss.
对9例无Pick小体的非典型Pick病进行了免疫组织化学研究。泛素（ub）阳性而tau阴性的结构主要见于大脑皮质和海马齿状回。在大脑皮质，大多数ub阳性结构在神经毡中有ub阳性树突，尽管有些在神经元胞质中也显示弥漫性ub阳性染色。这些ub阳性结构分布于整个II - IIIab层和V - VI层。齿状回颗粒细胞有ub阳性的神经元内包涵体。当根据大脑皮质神经元丢失程度评估ub阳性神经元和树突的数量时，在神经元丢失非常轻微的区域，ub阳性神经元数量显著较低，而在神经元丢失中度的区域则较高。相比之下，即使在神经元丢失非常轻微的皮质区域也能检测到ub阳性树突。免疫电镜下，ub阳性结构在神经元胞质和树突中含有ub阳性的核糖体样颗粒成分，这些成分偶尔与粗面内质网相关，并伴有一些丝状成分。在双重免疫染色法中，几乎所有ub阳性结构对ub结合蛋白p62呈阳性。大脑皮质中一些ub阳性或阴性神经元用抗ub连接酶（Parkin）和抗ub C末端水解酶抗体呈阳性免疫标记，而树突未被这些抗体标记。从本研究结果提示，在大脑皮质，这些泛素化蛋白可能在神经元变性开始时首先在树突中积聚，然后出现在神经元胞质中，最终随着神经元丢失而消失。
