Brain Aging : Pathogenesis from the cerebral β amyloid deposition to the development of the dementia.
脑老化:从大脑β淀粉样蛋白沉积到痴呆发展的发病机制。
基本信息
- 批准号:10832004
- 负责人:
- 金额:$ 2.05万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:1998
- 资助国家:日本
- 起止时间:1998 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
To know how Alzheimer's disease develops from the cerebral β amyloid deposition, which is frequently seen in the non-demented elderly people, we have collected autopsied brains and formed the Gunma Senile Brain Bank. We have measured the amounts of deposited Aβ by ELISA as well as evaluated them by immunohistochemistry. We found that cerebral β amyloid deposition precedes the abnormal accumulation of phosphorylated tau. We also analyzed ApoE genotypes, and found that ApoE4 promotes earlier beginning of the cerebral β amyloid deposition.We further studied the ultrastructural localization of β protein in the early stage of amyloid deposition, and found that β protein starts to deposits on a part of the cell surface plasma membrane as membrane-bound Aβ. Flotillin, a marker protein of the cerebral DIG/caveolae, was found diffusely in the cerebral cortex, and the amounts of it increased according to the degree of the cerebral β amyloid deposition.We also studies the ultrastructural localization of β-amyloid-related proteins, amyloid β protein precursor(APP)and β amyloid cleaving enzyme(BACE), and found that these proteins localize to the cytoplasmic vesicles.
为了了解阿尔茨海默病是如何从非痴呆老年人大脑中常见的β淀粉样沉积发展而来的,我们收集了尸检的大脑,成立了群马老年脑库。用ELISA法测定Aβ的沉积量,并用免疫组织化学方法对其进行评价。我们发现,大脑β淀粉样蛋白沉积先于磷酸化tau的异常积聚。我们还分析了载脂蛋白E的基因类型,发现载脂蛋白E4促进了脑β淀粉样蛋白沉积的早期开始。我们进一步研究了β蛋白在淀粉样蛋白沉积早期的超微结构定位,发现β蛋白以膜结合型Aβ的形式开始沉积在细胞表面质膜的一部分。Flotillin是大脑Dig/Caveolae的标志性蛋白,广泛分布于大脑皮层,其含量随大脑β淀粉样蛋白沉积程度的增加而增加。我们还研究了β淀粉样蛋白相关蛋白、淀粉样蛋白前体和β淀粉样裂解酶的超微结构定位,发现这些蛋白定位于细胞质中的小泡。
项目成果
期刊论文数量(36)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kasa P, Papp H, Kovacs I, Forgon M, Penke B, Yamaguchi H: "Human amyloid-β1-42 applied in vivo inhibits the fast axonal transport of proteins in the sciatic nerve of rat."Neurosci Lett. 278. 117-119 (2000)
Kasa P、Papp H、Kovacs I、Forgon M、Penke B、Yamaguchi H:“体内应用的人淀粉样蛋白-β1-42 抑制大鼠坐骨神经中蛋白质的快速轴突转运。”Neurosci Lett。 119(2000)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Maat-Schieman ML, Yamaguchi H, van Duinen SG, Natte R, Roos RA: "Age-related plaque morphology and C-terminal heterogeneity of amyloid β in Dutch-type hereditary cerebral hemorrhage with amyloidosis"Acta Neuropathol. 99. 409-19 (2000)
Maat-Schieman ML、Yamaguchi H、van Duinen SG、Natte R、Roos RA:“荷兰型遗传性脑出血伴淀粉样变性中淀粉样蛋白 β 的年龄相关斑块形态和 C 末端异质性”Acta Neuropathol。 (2000)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Natte R,et al: "Ulta-structural evidence of early non-fibrillar Aβ42 in the capiltary basement membrane of patients with hereditary cerebral hemorrhage with amyloidosis,Dutch type"Acta Neuropathol.. 98. 577-582 (1999)
Natte R 等人:“荷兰型遗传性脑出血伴淀粉样变性患者毛细血管基底膜中早期非纤维状 Aβ42 的超结构证据”Acta Neuropathol.. 98. 577-582 (1999)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Morishima-Kawashima M, Oshima N, Ogata H, Yamaguchi H, Yoshimura M, Sugihara S, Ihara Y: "Effect of apolipoprotein E allele ε4 on the initial phase of amyloid β-protein accumulation in the human brain."Am J Pathol. 157. 2093-2099 (2000)
Morishima-Kawashima M、Oshima N、Ogata H、Yamaguchi H、Yoshimura M、Sugihara S、Ihara Y:“载脂蛋白 E 等位基因 ε4 对人脑中淀粉样 β 蛋白积累初始阶段的影响。”Am J Pathol。 157. 2093-2099 (2000)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Yamaguchi H. et al: "Amyloid β protein (Aβ) starts to deposit as plasma membrane-bound form in diffuse plaques of brains."J Neuropathol Exp Neurol. 59. 723-732 (2000)
Yamaguchi H. 等人:“β 淀粉样蛋白 (Aβ) 开始以质膜结合形式沉积在大脑的弥漫性斑块中。”J Neuropathol Exp Neurol. 59. 723-732 (2000)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
YAMAGUCHI Haruyasu其他文献
YAMAGUCHI Haruyasu的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('YAMAGUCHI Haruyasu', 18)}}的其他基金
Creation of rehabilitation for dementia
建立痴呆症康复
- 批准号:
22650123 - 财政年份:2010
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Pathology of the Alzheimer disease : prevention of cerebral β-amyloid deposition
阿尔茨海默病的病理学:预防大脑β-淀粉样蛋白沉积
- 批准号:
19300122 - 财政年份:2007
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Research on cerebral beta-amyloid deposition and neurodegeneration related to lipid metabolism of the plasma membrane.
质膜脂质代谢相关脑β-淀粉样蛋白沉积及神经退行性变的研究。
- 批准号:
16300110 - 财政年份:2004
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Influence of membrane lipid metabolism on cerebral amyloid deposition and neurodegeneration.
膜脂代谢对脑淀粉样蛋白沉积和神经退行性变的影响。
- 批准号:
13480250 - 财政年份:2001
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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 - 财政年份:1996
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
相似国自然基金
新型F-18标记香豆素衍生物PET探针的研制及靶向Alzheimer's Disease 斑块显像研究
- 批准号:81000622
- 批准年份:2010
- 资助金额:20.0 万元
- 项目类别:青年科学基金项目
阿尔茨海默病(Alzheimer's disease,AD)动物模型构建的分子机理研究
- 批准号:31060293
- 批准年份:2010
- 资助金额:26.0 万元
- 项目类别:地区科学基金项目
跨膜转运蛋白21(TMP21)对引起阿尔茨海默病(Alzheimer'S Disease)的γ分泌酶的作用研究
- 批准号:30960334
- 批准年份:2009
- 资助金额:22.0 万元
- 项目类别:地区科学基金项目
相似海外基金
Discovering early biomarkers of Alzheimer's disease using genetic and physics-informed networks
利用遗传和物理信息网络发现阿尔茨海默病的早期生物标志物
- 批准号:
2904538 - 财政年份:2024
- 资助金额:
$ 2.05万 - 项目类别:
Studentship
Deciphering electrophysiological Alzheimer's Disease biomarkers for early diagnosis using interpretable deep learning
使用可解释的深度学习破译电生理阿尔茨海默病生物标志物以进行早期诊断
- 批准号:
24K18602 - 财政年份:2024
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Investigating And Targeting Microglial Senescence In Alzheimer's Disease
研究并针对阿尔茨海默病中的小胶质细胞衰老
- 批准号:
MR/Y004116/1 - 财政年份:2024
- 资助金额:
$ 2.05万 - 项目类别:
Research Grant
DMS/NIGMS 1: Multilevel stochastic orthogonal subspace transformations for robust machine learning with applications to biomedical data and Alzheimer's disease subtyping
DMS/NIGMS 1:多级随机正交子空间变换,用于稳健的机器学习,应用于生物医学数据和阿尔茨海默病亚型分析
- 批准号:
2347698 - 财政年份:2024
- 资助金额:
$ 2.05万 - 项目类别:
Continuing Grant
Histone variant macroH2A1 as a novel regulator of memory deficits in Alzheimer's disease
组蛋白变体 MacroH2A1 作为阿尔茨海默病记忆缺陷的新型调节剂
- 批准号:
478226 - 财政年份:2023
- 资助金额:
$ 2.05万 - 项目类别:
Operating Grants
Incorporating Diversity in Alzheimer's Disease Research: Developing Representative and Generalizable models
将多样性纳入阿尔茨海默病研究:开发代表性和可推广的模型
- 批准号:
495662 - 财政年份:2023
- 资助金额:
$ 2.05万 - 项目类别:
Operating Grants
Development of novel macrocyclic BACE1 inhibitors for preventive or therapeutic agents for Alzheimer's disease
开发用于预防或治疗阿尔茨海默病的新型大环 BACE1 抑制剂
- 批准号:
23K06058 - 财政年份:2023
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Fluency from Flesh to Filament: Collation, Representation, and Analysis of Multi-Scale Neuroimaging data to Characterize and Diagnose Alzheimer's Disease
从肉体到细丝的流畅性:多尺度神经影像数据的整理、表示和分析,以表征和诊断阿尔茨海默病
- 批准号:
10462257 - 财政年份:2023
- 资助金额:
$ 2.05万 - 项目类别:
Computational modelling of disease progression and subtype discovery in Alzheimer's Disease
阿尔茨海默病疾病进展和亚型发现的计算模型
- 批准号:
2885305 - 财政年份:2023
- 资助金额:
$ 2.05万 - 项目类别:
Studentship
The Contribution of Mitochondrial Dysfunction to Alzheimer's disease
线粒体功能障碍对阿尔茨海默病的影响
- 批准号:
2886872 - 财政年份:2023
- 资助金额:
$ 2.05万 - 项目类别:
Studentship