Development and clinical application of novel methods for diagnosis and therapy of Alzheimer disease by regulation of neurotoxic oligomer

通过调节神经毒性寡聚物诊断和治疗阿尔茨海默病的新方法的开发和临床应用

• 批准号: 19390233
• 负责人: SHOJI Mikio
• 金额: $ 11.32万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19390233/
• 关键词: 神経病態生化学; アルツハイマー病; オリゴマー; 診断; 治療; 臨床応用

Recent studies suggest that oligomers are direct pathogenic agents to cause synaptic and neuronal disturbance in dementia patients including Alzheimer's disease. In this study, we established special antibodies to Ass, tau and α-synuclein to develop ELISA and detection systems, showing soluble oligomers, naturally occurred anti-Ass antibodies in brains and CSF in AD patients. Model mice of DLB (TgSNY) and AD (2xTgTau+/-APP+/-) were established. The pathological cascades of Ass induced tauopathy using 2xTgTau+/-APP+/- and NFT formation and neuronal cell deaths using by micro arrays were elucidated. Many biological pathways involved in these final cascades. Administration of anti-Ass antibodies reduced Ass burden and Ass oligomer in mice brains and increased in Ass monomer in CSF and plasma. Thus, anti-oligomer therapy is a possible agent for cure of neurodegenerative dementia.

最近的研究表明，寡聚体是导致痴呆患者包括阿尔茨海默病的突触和神经元紊乱的直接致病因子。在本研究中，我们建立了针对Ass、tau和α-synuclein的特异性抗体，以开发ELISA和检测系统，显示AD患者脑和CSF中的可溶性寡聚体、天然存在的抗Ass抗体。建立DLB（TgSNY）和AD（2xTgTau+/-APP+/-）模型小鼠。通过微阵列阐明了使用2xTgTau+/-APP+/-和NFT形成和神经元细胞死亡的Ass诱导的tau蛋白病的病理级联。许多生物途径参与了这些最后的级联反应。施用抗Ass抗体降低小鼠脑中的Ass负荷和Ass寡聚体，并增加CSF和血浆中的Ass单体。因此，抗寡聚体疗法是治疗神经退行性痴呆的可能药剂。

项目成果

The Japanese Genetic Study Consortium for Alzheimer's Disease, Consortium Information : Members are listed in the acknowledgements. Genetic association of CTNNA3 with late-onset Alzheimer's disease in females

日本阿尔茨海默病基因研究联盟，联盟信息：成员列于致谢中。

• 发表时间: 2007
• 期刊: Hum Mol Genet 16(23)
• 作者: Miyashita A;Arai H;Asada T;Imagawa M;Matsubara E;Shoji M;Higuchi S;Urakami K;Kakita A;Takahashi H;Toyabe S;Akazawa K;Kanazawa I;Ihara Y;Kuwano R
• 通讯作者: Kuwano R

アルツハイマー病の検査法, アルツハイマー病に対して治療効果を有する物質のスクリーニング方法およびアルツハイマー病の検査キット

阿尔茨海默病的检测方法、对阿尔茨海默病有治疗作用的物质的筛选方法以及阿尔茨海默病的检测试剂盒

• 发表时间: 2010

Components of Lewy bodies.

路易体的组成部分。

• 发表时间: 2007
• 作者: 木村朋寛;石川謙介;西村有起;Schatzl HM;堂浦克美;Mikio Shoji
• 通讯作者: Mikio Shoji

Increased ER stress during motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis

• DOI: 10.1179/016164107x229803
• 发表时间: 2007-12-01
• 期刊: NEUROLOGICAL RESEARCH
• 影响因子: 1.9
• 作者: Nagata, Tetsuya;Ilieva, Hristelina;Abe, Koji
• 通讯作者: Abe, Koji

Immune response to Aβ40 and Aβ42 in normal controls and patients with Alzheimer's disease

正常对照和阿尔茨海默病患者对 Aβ40 和 Aβ42 的免疫反应

• 发表时间: 2009
• 作者: Iijima M;Koike H;Hattori N;Tamakoshi A;Katsuno M;Tanaka F;Yamamoto M;Arimura K;Sobue G.;河野 修興;Mikio Shoji
• 通讯作者: Mikio Shoji