PT -期刊文章盟Hyun-Sik杨盟Lei Yu -查尔斯白色盟盟- Lori Chibnik盟朱莉施耐德AU -大卫·班尼特盟菲利普De Jager TI -染色体位点的识别影响认知弹性神经病理学(S21.003) DP - 2016年4月05 TA -神经病学PG - S21.003 VI - 86 IP - 16补充4099 - //www.ez-admanager.com/content/86/16_Supplement/S21.003.short 4100 - //www.ez-admanager.com/content/86/首页16_Supplement/S21.003.full所以Neurology2016 4月05;86 AB -目的:我们旨在发现遗传因素的认知神经病理学的韧性。背景:认知弹性归因于大脑储备能力,认知储备,微分组织病理反应。此外,病态不经常占会引起明显的韧性。然而,遗传决定因素的认知弹性是未知的。方法:我们研究的一个子集参加宗教团体学习和拉什记忆和衰老项目(n = 979)。我们定义术语“剩余认知”是认知之间的差异直接死亡和认知的人口结构和常见neuropathologic指数预测的阿尔茨海默氏症、脑血管疾病,路易的身体疾病,和海马硬化。残余的认知,进行了全基因组关联研究和基因在100 kb的暗示位点(术中;10 ^ 5),甲基化状态与残余认知测试。最后,这些暗示位点是否cis-expressive数量性状基因座(cis-eQTL)检查。结果:共8暗示染色体位点,这些位点和基因在100 kb: WARS2, UNC5C, MTHFD1L, AKAP12, VWDE, TMEM106B, AGR2 AGR3, DLGAP2。 Among these, WARS2, UNC5C, AKAP12, AGR2, and DLGAP2 had permuted methylation status associated with residual cognition. The minor allele for TMEM106B locus (top SNP rs11509153G) was a cis-eQTL associated with a decrease in TMEM106B expression. Interestingly, AKAP12 and DLGAP2 are synaptic proteins with implications in cognitive reserve, while UNC5C contributes to neuronal vulnerability to neurotoxins. The TMEM106B locus (rs11509153G) was in strong linkage disequilibrium with a previously identified protective variant (rs1990622G) for TDP-43, a pathology that has not been routinely accounted for. Conclusions: We identified several chromosomal loci where evidences from genetic and epigenetic factors converge to suggest association with apparent cognitive resilience (measured as residual cognition), and in proximity to these loci are genes involved in synaptic function, neuronal vulnerability, and TDP-43 pathology.Disclosure: Dr. Yang has nothing to disclose. Dr. White has nothing to disclose. Dr. Yu has nothing to disclose. Dr. Chibnik has nothing to disclose. Dr. Schneider has received personal compensation for activities with AVID Radiopharmaceuticals, Inc. and GE Healthcare. Dr. Bennett has received personal compensation for activities with Danone, Inc., Dr. Willmar Schwabe Pharmaceuticals, KG Pharmaceuticals and Eli Lilly, Inc. as a consultant. Dr. De Jager has received research support from Biogen Idec and Genzyme.Monday, April 18 2016, 1:00 pm-3:00 pm