| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
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.
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