The molecular mechanism for Aβ oligomer hypothesis in Alzheimer's disease

Aβ寡聚体假说在阿尔茨海默病中的分子机制

• 批准号: 21390271
• 负责人: MORI Hiroshi
• 金额: $ 11.48万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390271/
• 关键词: アミロイド; 遺伝変異; モデルマウス; 認知症; 遺伝異変

We here provided in vivo and in vitro evidence to support Aβ oligomer hypothesis that is widely believed to be the most reliable idea to understand Alzheimer's disease. To verify its certification, we examined not only patients with familial AD by clinical and brain imaging analyses but also a new mouse model bearing solely Aβ oligomer. We found the abnormal accumulation of intraneuronal Aβ oligomer as a beginning pathological change. Thus more concern must be concentrated on Aβ oligomer to develop its measurement for the precise diagnosis and the treatment for the proper medication.

我们发现神经元Aβ低聚物假设的异常积累，这被认为是了解阿尔茨海默氏病的最可靠的想法。为了验证其认证，我们不仅检查了临床和脑成像分析的家庭AD患者，而且还检查了仅带有Aβ低聚物的新小鼠模型。我们发现神经元Aβ低聚物的异常积累是一种开始病理变化。必须将更多的关注点集中在Aβ低聚物上，以开发其用于精确诊断和适当药物治疗的测量。

项目成果

Pittsburgh Compound B-Negative Dementia-A Possibility of Misdiagnosis of Patients With Non-AlzheimerDisease-Type Dementia as Having AD

匹兹堡复合 B-阴性痴呆-非阿尔茨海默病型痴呆患者误诊为 AD 的可能性

• DOI: 10.1177/0891988711409410
• 发表时间: 2011
• 期刊: Journal of Geriatric Psychiatry and Neurology
• 影响因子: 2.6
• 作者: Shimada H;Ataka S;Takeuchi J;Mori H;Wada Y;Watanabe Y;Miki T
• 通讯作者: Miki T

The E693Delta mutation in amyloid precursor protein increases intracellular accumulation of amyloid beta oligomers and causes endoplasmic reticulum stress-induced apoptosis in cultured cells

淀粉样前体蛋白的 E693Delta 突变增加了淀粉样β寡聚体的细胞内积累，并导致培养细胞中内质网应激诱导的细胞凋亡

• 发表时间: 2009
• 期刊: The American journal of pathology
• 作者: Nishitsuji K;Tomiyama T;Ishibashi K;Ito K;Teraoka R;Lambert MP;Klein WL & Mori H
• 通讯作者: Klein WL & Mori H

Cliniical Course of Patients with Familial Early-Onset Alzheimer's Disease Potentially Lacking Senile Plaques Bearing the E693delta Mutation in Amyloid Precursor Protein

可能缺乏带有淀粉样前体蛋白 E693delta 突变的老年斑块的家族性早发性阿尔茨海默病患者的临床病程

• 发表时间: 2011
• 期刊: Dement Geriatr Cogn Disord
• 作者: Shimada H;Ataka S;Toomiyama T;Takeuchi H;Mori H;& Miki T
• 通讯作者: & Miki T

Regulation of cholesterol efflux by amyloid b secretion(Aβ分泌によるコレステロールeffluxの制御)

通过淀粉样蛋白 b 分泌调节胆固醇流出（通过 Aβ 分泌控制胆固醇流出）

• 发表时间: 2009
• 作者: Noriyuki Matsuda;Shigeto Sato;Kahori Shiba;Kei Okatsu;Keiko Saisho;Clement A Gautier;Yu-shin Sou;Shinji Saiki;Sumihiro Kawajiri;Fumiaki Sato;Mayumi Kimura;Masaaki Komatsu;Nobutaka Hattori;Keiji Tanaka;山中宏二;梅田知宙
• 通讯作者: 梅田知宙

Intraneuronal Amyloid β Oligomers Cause Cell Death Via Endoplasmic Reticulum Stress, Endosomal/Lysosomal Leakage, and Mitochondrial Dysfunction In Vivo

• DOI: 10.1002/jnr.22640
• 发表时间: 2011-07-01
• 期刊: JOURNAL OF NEUROSCIENCE RESEARCH
• 影响因子: 4.2
• 作者: Umeda, Tomohiro;Tomiyama, Takami;Mori, Hiroshi
• 通讯作者: Mori, Hiroshi