PT -期刊文章盟Van决断Blitterswijk AU -妮可·芬奇盟马修·贝克AU -雪王盟-凯文Bieniek AU -玛丽Dejesus-Hernandez AU -塔尼亚Gendron盟燕Asmann AU -迈克尔·赫克曼AU -帕特里夏·布朗AU -基思·约瑟夫AU -约瑟夫·帕里盟David Knopman AU -罗纳德·彼得森AU -伦纳德Petrucelli盟-布拉德利Boeve AU -尼尔Graff-Radford AU -凯文Boylan AU -丹尼斯·迪克森盟罗莎说Rademakers TI -转体基因的潜在生物标记< em > C9ORF72 < / em >有关的疾病(S33.001) DP - 2015年4月06 TA -神经病学PG - S33.001 VI - 84 IP - 14补充4099 - //www.ez-admanager.com/content/84/14_Supplement/S33.001.short 4100 - //www.ez-admanager.com/content/84/14_Supplement/S33.001.full所以Neurology2015 4月06;首页84 AB -目的:识别重复扩张所导致的疾病的生物标记在染色体9 72年开放阅读框(C9ORF72)。背景:迄今为止,在C9ORF72 GGGGCC-repeat扩张是最常见的两个致命的神经退行性疾病的遗传原因:额颞叶痴呆(FTD)和运动神经元病(MND)。不存在有效的生物标志物来诊断C9ORF72-related疾病,预测疾病进展,或监视潜在疗法的效果。设计/方法:我们大脑执行第一个全基因组表达分析在C9ORF72扩张运营商使用全基因组DASL HT化验(Illumina公司)。我们的研究群体由C9ORF72扩张运营商(n = 32)以及疾病控制(n = 30)和控制无神经系统疾病(n = 20)。另外,我们采用定量实时PCR、酶联免疫吸附试验(ELISA)和免疫印迹技术。结果:我们发现转体基因(竞技场队伍)显著上调小脑当比较C9ORF72扩张运营商对疾病控制(叠化= 5.7;假定值= 5.0 e-04)或控制没有神经系统疾病(叠化= 7.4;假定值= 4.3 e-04)。 TTR up-regulation was validated using quantitative real-time PCR, which confirmed the up-regulation in C9ORF72 expansion carriers (n=44) as compared to disease controls (n=30; p-value=4.5e-06) and to controls without neurological diseases (n=20; p-value=2.1e-05), but also as compared to patients with other diseases, such as Alzheimer’s disease (n=20; p-value=7.9e-06) and progressive supranuclear palsy (n=20; p-value=5.2e-04). Our findings, therefore, indicate that TTR up-regulation is specific to C9ORF72-related diseases. Moreover, we demonstrated that the changes in RNA levels of TTR are reflected by changes in its protein levels in the cerebellum, plasma, and cerebrospinal fluid (CSF). CONCLUSIONS: Based on our findings, TTR may serve as a biomarker for C9ORF72-related diseases, and additionally, could help to unravel biomarker patterns in sporadic diseases. Furthermore, our identification of TTR, which has neuroprotective effects, might also point towards compensatory mechanisms that influence the presentation and/or progression of C9ORF72-related diseases, and that could uncover targets for new therapeutic approaches.Disclosure: Dr. Van Blitterswijk has nothing to disclose. Dr. Finch has nothing to disclose. Dr. Baker has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Bieniek has nothing to disclose. Dr. Dejesus-Hernandez has nothing to disclose. Dr. Gendron has nothing to disclose. Dr. Asmann has nothing to disclose. Dr. Heckman has nothing to disclose. Dr. Brown has nothing to disclose. Dr. Josephs has nothing to disclose. Dr. Parisi has nothing to disclose. Neurology, Deputy Editor, Dr. Petersen has received personal compensation for activities with Pfizer Inc. and Janssen Alzheimer's Immunotherapy. Dr. Petrucelli has nothing to disclose. Dr. Boeve has received research support from GE Healthcare. Dr. Graff-Radford has received personal compensation for activities with Codman and Cytox as a scientific advisory board member or a consultant. Dr. Graff-Radford has received royalty payments for UpToDate. Dr. Boylan has received research support from Biogen Idec, Cytokinetics, Inc., and Neuraltus Pharmaceuticals, Inc. Dr. Dickson has nothing to disclose. Dr. Rademakers has nothing to disclose.Wednesday, April 22 2015, 4:00 pm-5:45 pm