% 0期刊文章%一个范Blitterswijk %决断妮可·芬奇%马修·贝克%一个凯文Bieniek雪王% %一个玛丽Dejesus-Hernandez %一个塔尼亚Gendron %燕Asmann % Patricia布朗迈克尔·赫克曼% %一个约瑟夫·帕里基思·约瑟夫% %一个伦纳德罗纳德·彼得森David Knopman % % Petrucelli %一个尼尔Graff-Radford布拉德利Boeve % %丹尼斯·迪克森凯文Boylan % %罗莎说Rademakers % T转体基因的潜在生物标志物C9ORF72有关的疾病(S33.001) % D J神经病学2015% % P S33.0首页01 % V 84% N % X 14补充目的: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)。老年病竞技场队伍使用定量实时PCR验证,证实了老年病C9ORF72扩张运营商(n = 44)与疾病控制(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 %U