| Project/Area Number |
63570504
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Osaka University |
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Principal Investigator |
TAKEDA Masatoshi Osaka University Medical School Joshu, 医学部, 助手 (00179649)
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| Co-Investigator(Kenkyū-buntansha) |
TADA Kunitoshi Osaka University Medical School Assistant Professor, 医学部, 講師 (80135681)
HARIGUCHI Shiro Osaka University Medical School Associate Professor, 医学部, 助教授 (10028459)
NISHIMURA Tsuyoshi Osaka University Medical School Professor, 医学部, 教授 (70028455)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1988: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Alzheimer's Disease / Intermediate Filament / Cytoskeleton / Aluminium / Glial Fibrillary Acidic Protein / Vimentin / Neurofilament / Fibroblast / ビメンチン / フォドリン / 中間径線維 / マイクロチュブル / マイクロフィラメント / 診断法 / ニューロフィラメント / 蛋白分解酵素 / ライソゾーム / カテプシンD / 神経原線維変化 / アルツハイマー病 |
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| Research Abstract |
Changes in cytoskeletal proteins with Alzheimer's disease and investigated and the following experimental data have been obtained.
1. Experimental neurofibrillary changes by aluminium intoxication The production of 10 nm filaments in the brain of aluminium intoxicated rabbit brain was studied. The accumulated 10 nm filaments are composed of neurofilament proteins and the accumulation is partly due to overproduction of neurofilament subunit proteins and partly by impaired activity of degradating enzymes. Accumulated neurofilament proteins are overphosphorylated. It is indicated dislocalization of neurofilament protein from axons to neural soma or dendrites is the main pathological process in aluminium intoxicated brain.
2. Antibody titer against glial fibrillary acidic protein (GFAP) Autoantibody titer to cytoskeletal protein in sera from Alzheimer's disease patients were studied. Higher antibody titer to GFAP is shown with Alzheimer's disease serum. The high titer of this antibody is a useful biological marker of diagnosis of Alzheimer's disease.
3. Cytoskeletal aberration of Alzheimer fibroblasts Fibroblasts cultured from Alzheimer's disease patients were studied. The decreased efficiency in adhesion was demonstrated with Alzheimer fibroblasts. Vimentin distribution in Alzheimer fibroblasts were aberrated and some pathological process is indicated which affects cell adhesion and the distribution of the cytoskeletons.
4. Fluorometric method to measure the degree of assembly of intermediate filaments have been developed. Assembly kinetics of GFAP was studied and it is shown that this newly developed method produces reliable evaluation of the degree of assembly of GFAP on the real time basis.
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