Study for novel biomarkers for Alzheimer's disease

阿尔茨海默病的新型生物标志物研究

• 批准号: 23659450
• 负责人: SHOJI Mikio
• 金额: $ 2.25万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659450/
• 关键词: 神経分子病態学; 神経内科学; 神経科学; 臨床神経学; アルツハイマー病; バイオマーカー

To facilitate early diagnosis of AD dementia and other non-AD dementias, simple and quick assay of CSF and plasma biomarkers for Alzheimer disease and non-AD dementia were studied and developed. 1) To identify presence of plasma tau and p-tau, anti-human CNS tau antibodies (tauA/tauB) were developed. Western blot analysis of immunoprecipitated samples from CSF and plasma of TgtauP301L mice using tauA/tauB revealed the real presence of metabolized tau fragments from CNS and PNS. Further confirmation of the presence of CNS tau was necessary. Basic evaluation of CSF and plasma α-synuclein showed adequate reproducibility and sensitivity. Measurements of 105 cases of AD and non-AD dementias showed that increased levels of MCI, and other neurological diseases CSF As40，As42, tauおよび血液As40，As42測定値in AD, MCI, and controls, but, decreased levels of α-synuclein in Parkinson diseases. The levels of CSF As40, As42, tau andplasma As40，As42were correlated with those levels of α-synuclein. High sensitive ELISA of TDP-43 are developing. Candidate 28 molecules as Alzheimer disease identified by proteomics analysis of CSF proteins with more than 30,000 kD were further evaluated using bioinformatics data base for patent filing.

To facilitate early diagnosis of AD dementia and other non-AD dementias, simple and quick assay of CSF and plasma biomarkers for Alzheimer disease and non-AD dementia were studied and developed. 1) To identify presence of plasma tau and p-tau, anti-human CNS tau antibodies (tauA/tauB) were developed. Western blot analysis of immunoprecipitated samples from CSF and plasma of TgtauP301L mice using tauA/tauB revealed the real presence of metabolized tau fragments from CNS and PNS. Further confirmation of the presence of CNS tau was necessary. Basic evaluation of CSF and plasma α-synuclein showed adequate reproducibility and sensitivity. Measurements of 105 cases of AD and non-AD dementia showed that increased levels of MCI, and other neurological diseases CSF As40, As42, tau The levels of CSF As40, As42, tau andplasma As40，As42were correlated with those levels of α-synuclein. High sensitive ELISA of TDP-43 are developing. Candidate 28 molecules as Alzheimer disease identified by proteomics analysis of CSF proteins with more than 30,000 kD were further evaluated using bioinformatics data base for patent filing.

项目成果

アルツハイマー病のバイオマーカー

阿尔茨海默病生物标志物

• 发表时间: 2008
• 期刊: カレントテラピー 26
• 作者: 渡辺光法;瓦林毅;冨山誠彦;東海林幹夫
• 通讯作者: 東海林幹夫

認知症：神経心理学的アプローチ

痴呆症：一种神经心理学方法

• 发表时间: 2012
• 作者: Izumi Y;Miyamoto R;Morino H;Yoshizawa A;Nishinaka K;Udaka F;Kameyama M;Maruyama H;Kawakami H;東海林幹夫
• 通讯作者: 東海林幹夫

脳アミロイドーシスに対するAs免疫療法.アミロイドーシスuptodate

作为脑淀粉样变性的最新免疫疗法。

• 发表时间: 2011
• 作者: Shimizu F;Sano Y;Takahashi T;Haruki H;Saito K;Koga M;Kanda T;東海林幹夫
• 通讯作者: 東海林幹夫

アルツハイマー病と軽度認知障害の発症予測スクリーニングマーカーの検証

验证用于预测阿尔茨海默病和轻度认知障碍发病的筛选标记

• 作者: 藤岡祐介;石垣診祐;祖父江元;松原悦朗，高村歩美，若佐谷保仁，瓦林毅，東海林幹夫
• 通讯作者: 松原悦朗，高村歩美，若佐谷保仁，瓦林毅，東海林幹夫

DNA microarray解析による神経原線維変化の形成および神経細胞死に関する因子の解析

利用 DNA 微阵列分析与神经原纤维缠结形成和神经元细胞死亡相关的因素

• 作者: 金子佳賢;成田一衛;若佐谷保仁，瓦林毅，松原悦朗，東海林幹夫
• 通讯作者: 若佐谷保仁，瓦林毅，松原悦朗，東海林幹夫