Study of the developing mechanism of dementia in non-Alzheimer-type degenerative dementias

在非阿尔茨海默型退行性痴呆的研究中，对弥漫性路易体病(DLBD)以及不典型的Pick病和进行性核上性瘫痪(PSP)进行了研究。在DLBD的第一项研究中，海马区的许多泛素阳性结构是由穿支通路的末端轴突退化引起的。这些结构也是α-突触核蛋白免疫反应阳性的，在免疫电子显微镜下含有与路易小体相似的丝状成分，这表明α-突触核蛋白聚集成细胞骨架成分的过程首先发生在终末轴突中，在起始细胞形成LB之前，是一个“死后”的退化过程。在DLBD的第二个研究中，在DLBD和阿尔茨海默病(AD)边缘区的同一神经元中，经常同时存在LB和神经纤维缠结(NFT)。α-突触核蛋白阳性的细丝成分与成对螺旋丝之间不存在连续性，提示Lb和NFT是分开发育的。相反，在AD中，这两个组分之间存在密切的连续性，表明α-突触核蛋白的聚集发生在NFT形成之后。在无Pick小体的非典型Pick病中，患侧大脑皮质可见泛素阳性树突，齿状回颗粒细胞可见泛素阳性的神经元内包涵体，提示非典型Pick病与其他类型的额颞叶痴呆(FTD)具有共同的发病机制。在PSP中，PSP根据tau阳性神经元的缠结形成分为两组：典型PSP组和类似皮质基底性变性(CBD)的不典型PSP组，PSP中的NFT由PSP-NFT组成，而AD-NFT甚至在PSP和AD的共同好发部位也由PSP-NFT组成。

In the study of non-Alzheimer-type degenerative dementias, diffuse Lewy body disease(DLBD) as well as atypical Pick's disease and progressive supranuclear palsy(PSP) were investigated. In the first study of DLBD, many of the ubiquitin-positive structures in the hippocampus were caused by degeneration of terminal axons of the perforant pathway. These structures were also α-synuclein- immunoreactive, and contained similar filamentous components to those of Lewy bodies(LB) immunoelectron microscopically, suggesting that the aggregation of α-synuclein into cytoskeletal components first occurs in the terminal axons by a "dying back" degenerating process before the formation of LB in the origin cells. In the second study of DLBD, LB and neurofibrillary tangles(NFT) frequently coexisted in the same neurons of the limbic areas of DLBD and Alzheimer's disease(AD). There was no continuity between α-synuclein-positive filamentous components and paired helical filaments(PHF) in DLBD, suggesting that LB and NFT are developed separately. In contrast, there was the close continuity between the two components in AD, suggesting that the aggregation of α-synuclein occurs secondary to the NFT formation. In atypical Pick's disease without Pick bodies, there were ubiquitin-positive dendrites in the affected cerebral cortex and ubiquitin-positive intraneuronal inclusions in the granular cells of the dentate gyrus, suggesting that atypical Pick's disease shares common pathomechanism to that of other types of frontotemporal dementia(FTD). In PSP, PSP was divided into two groups according to the tangle-formation in tau-positive neurons; the group with typical PSP pathology and the group with atypical PSP pathology similar to corticobasal degeneration(CBD), and NFT in PSP consisted of PSP-NFT but not AD-NFT even in the common predilection sites of PSP and AD.