Brain aging : enhancing and suppressing factors of beta amyloid deposition

脑老化：β淀粉样蛋白沉积的增强和抑制因素

• 批准号: 08838004
• 负责人: YAMAGUCHI Haruyasu
• 金额: $ 1.34万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08838004/
• 关键词: Alzheimer's disease; dementia; amyloid-beta; apolipoprotein E; brain bank; brain aging; dementia; aging

We did the following research works to reveal the enhancing and suppressing factors of cerebral beta amyloid deposition.We corrected more than 40 brains from non-demented middle-aged subjects, and formed the Gunma Brain Bank. The samples from these brains were sent to several research institutes and universities, and are used for the research works on brain aging.We immunostained the tissue sections from these brains, and revealed that cerebral beta amyloid deposition started in the fifth decades. We analyzed the Abeta species using 2 different kinds of antibodies directed to C-terminal end of Abeta, and found that Abeta42 was a major from in the early stage of cerebral beta amyloid deposition. Furthermore, we found Abeta-positive granules in astrocytes, which were associated with diffuse plaques. We suggest the positively that senile plaquse are removed by astrocytes.We also analyzed the genotype of apolipoprotein E gene, and found high frequency of _<epsilon>4 genotype in the subjects with cerebral beta amyloid deposition.We made antibodies directed to presenilin-1, a causative gene of the early-onset familial Alzheimer's disease, but found no relation between presenilin-1 immunoreactivity and beta amyloid deposition.

为了揭示大脑β淀粉样蛋白沉积的促进和抑制因素，我们进行了以下研究工作：对40多名非痴呆中年人的大脑进行了校正，并建立了群马脑库。从这些大脑中提取的样本被送到几个研究机构和大学，用于大脑衰老的研究工作。我们对这些大脑的组织切片进行免疫染色，发现大脑β淀粉样蛋白沉积开始于50年代。我们用两种不同的针对Abeta C-末端的抗体分析了Abeta的种类，发现Abeta 42是脑β淀粉样蛋白沉积早期的主要形式。此外，我们还发现星形胶质细胞中存在Abeta阳性颗粒，这些颗粒与弥漫性斑块相关。我们还分析了载脂蛋白E基因的基因型，发现β-<epsilon>淀粉样蛋白沉积者中基因型_ 4的频率较高，我们制备了早老素-1的抗体，但未发现早老素-1的免疫反应性与β-淀粉样蛋白沉积之间的关系。

项目成果

Sughihara, S, et al.: "Characteristics of cerebral β amyloid deposition in four non-demented patients intheir forties with a high ApoE4 allele frequency" Neuropathology. 17. 326-333 (1997)

Sughihara, S 等人：“四名四十多岁、具有高 ApoE4 等位基因频率的非痴呆患者的大脑 β 淀粉样蛋白沉积的特征”《神经病理学》17. 326-333 (1997)。

山口 晴保: "アルツハイマー病とアポリポタンパクE" 脳神経. 48. 981-990 (1996)

Haruyasu Yamaguchi：“阿尔茨海默病和载脂蛋白 E”《神经病学》48. 981-990 (1996)。

Yamaguchi H et al: "Preferential labeling of Alzheimer neuro-fibrillary tangles with antisera for tau protein kinase (TPK) I/glycogen synthase kinase-3beta and cyclin-dependent kinase 5, a component of TPK II." Acta Neuropathol. 92. 232-241 (1996)

Yamaguchi H 等人：“用 tau 蛋白激酶 (TPK) I/糖原合酶激酶 3beta 和细胞周期蛋白依赖性激酶 5（TPK II 的一个组成部分）的抗血清优先标记阿尔茨海默病神经原纤维缠结。”

Yamaguchi, H, et al: "Alzheimer's Disease:Biology Diagnosis and Therapeutics" Wiley, 831 (1997)

Yamaguchi, H 等人：“阿尔茨海默病：生物学诊断和治疗”Wiley，831 (1997)

Yamaguchi, H: "The Molecular Pathology of Alzheimer'sDisease" Harwood Academic Publishers(印刷中), (1998)

Yamaguchi, H：“阿尔茨海默病的分子病理学”Harwood 学术出版社（正在出版），（1998 年）