Study about Causes of Alzheimer disease

阿尔茨海默病的病因研究

• 批准号: 03454288
• 负责人: NISHIMURA Tsuyoshi
• 金额: $ 3.65万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454288/
• 关键词: Alzheimer disease; buffy coat; inoculation; neurofilament; hamster; amyloid protein; ubiquitin; phosphorylation; バッフィコート; ニューロフィラメント; 血小板; アミロイド蛋白; ユビキチン; 線維芽細胞; アルツハイマ-病; アミロイドβ蛋白前駆体; ニュ-ロフィラメント; タウ; PHF; バッフィ-コ-ト

Buffy coats from 4 members of a family with Alzheimer's disease and 2 genetically unrelated healthy subjects were inoculated into the hamster brain. Eighteen months after the inoculation, the brains were studied by immunostaining with antibodies against neurofilamentts, tau, ubiquitin, and paired-helical filaments (PHF) as well as by electron microscopy. Vacuolar or spongiform degeneration was minimum. Intense positive staining by antibodies against neurofilament 200K protein was demonstrataed in neuronal perikarya of the lower brain stem nucleus in the hamster inoculated with the buffy coats from the 2 patients whith Alzheimer's disease and 2 children of the patient, which was not observed in the hamster brain inoculated with the buffy coat from the control subjects. Electron microscopy revealed intracytoplasmic accumulation of 10-nm neurofilament-like fibers. The accumulated neurofilaments were positively stained by anti-tau and anti-ubiquitin, but not by anti-PHF.The neurons containing massive intracytoplasmic neurofilament accumulation resembled ballooned neurons in some degenerative diseases including Alzheimer's disease. The results indicate that the buffy coat obtained from the patients and members of a family with Alzheimer's disease contains a factor which produces intracytoplasmic accumulation of neurofilament like fibers in neurons of the lower brain stem nuclei.

将来自患有阿尔茨海默病的家庭的4名成员和2名遗传上不相关的健康受试者的血沉棕黄层接种到仓鼠脑中。接种后18个月，大脑进行了研究，免疫染色与抗神经元，tau蛋白，泛素，和成对螺旋丝（PHF），以及通过电子显微镜。肺泡或海绵状变性最小。接种2名阿尔茨海默病患者及其2名子女的血沉棕黄层的仓鼠脑中，下脑干核的神经元周核中抗神经丝200 K蛋白抗体呈强烈阳性染色，而接种对照组血沉棕黄层的仓鼠脑中未观察到这种情况。电子显微镜显示胞浆内积累的10纳米神经胶质样纤维。聚集的神经丝被抗tau蛋白和抗泛素染色阳性，但不被抗PHF染色。含有大量胞浆内神经丝聚集的神经元类似于包括阿尔茨海默病在内的一些退行性疾病中的气球样神经元。结果表明，从阿尔茨海默病患者和家族成员获得的血沉棕黄层含有一种因子，该因子在下脑干核神经元中产生神经丝样纤维的胞质内积聚。

项目成果

武田雅俊: "アルツハイマー病-アミロイドβ蛋白沈着メカニズムとアミロイドβ蛋白前駆体の突然変異の意義" 現代医療. 25(1). 23-30 (1993)

Masatoshi Takeda：“阿尔茨海默病 - β 淀粉样蛋白沉积的机制和 β 淀粉样蛋白前体突变的意义”现代医学 25(1)。

武田雅俊: "老人斑・アミロイドをめぐる研究" 治療. 75(7). 53-57 (1993)

Masatoshi Takeda：“老年斑和淀粉样蛋白的研究”75（7）（1993）。

M.Takeda, Y.Tatebayashi, S.Tanimukai, Y.Nakamura, T.Tanaka, T.Nishimura: "Immunohistological study of microtubule-associated protain 2 and ubiquitin in chronically aluminum-intoxicated rabbit brain." Acta Neuropathol(Berl). 82. 346-352 (1991)

M.Takeda、Y.Tatebayashi、S.Tanimukai、Y.Nakamura、T.Tanaka、T.Nishimura：“慢性铝中毒兔脑中微管相关蛋白 2 和泛素的免疫组织学研究。”

M.Takeda: "Inoculation study of Alzheimer buffy coat to hamster brain" Advance in Bioscience. 87. 325-326 (1993)

M.Takeda：“阿尔茨海默病血沉棕黄层接种仓鼠大脑的研究”生物科学进展。

西村 健: "老年期の精神障害" ライフ・サイエンス, 162 (1993)

Ken Nishimura：“老年精神障碍”生命科学，162（1993）