文摘
摘要目的:本研究的目的是调查环境的调制效应(即。,cognitive reserve as measured by education attainment) and genetic background (i.e.,TMEM106B多态性,rs1990622 T / C)灰质(GM)在一个大的主题发生前症状轴承FTD-related致病突变。
背景:额颞叶痴呆(FTD)是一种进行性神经退行性异构障碍大约三分之一的病例常染色体显性遗传。它最近被证明认知储备,以多年的正规教育,可能抵消持续的病理过程。此外,TMEM106b发现了基因型的遗传修饰符在疾病发病年龄FTD TDP-43病理患者。
设计/方法:231名参与者从GENFI研究包括:108无症状入库单,MAPT或C9orf72突变携带者和123非(遗传状态、GS = 1突变阳性,g = 0突变-)。对于每一个主题,皮层和皮层下通用卷使用的分割生成体积t1加权核磁共振大脑扫描。TMEM106b进行基因分型,多年的教育记录。我们首先获得一个复合测量graph-Laplacian通用卷的主成分分析,然后安装一个线性混合效应的交互模型,考虑的作用一)GS;b)教育程度;和c) TMEM106b通用卷上基因型。
结果:突变阳性(GS = 1)降低通用卷(P = 0.002)。教育直接影响通用g = 1和GS = 0组(P = 0.02)较低的教育水平是降低卷。TMEM106b基因型没有直接影响通用卷但GS = 1组调制斜率之间的关系教育和通用卷(P = 0.007)。
结论:总之,脑萎缩基因FTD发生前症状学科是由遗传和环境因素的影响。这些发现应该consideredin评估结果在未来疾病修饰试验
研究支持:遗传FTD倡议(GENFI)
披露:Premi博士没有披露。格拉希博士没有披露。范博士没有披露。Galimberti博士没有披露。格拉夫博士没有披露。Masellis博士已经与诺华收到个人补偿活动,Bioscape医学成像,通用电气医疗集团,联合制药。塔尔塔利亚博士没有披露。Tagliavini博士没有披露。罗博士已经收到个人补偿活动与莉莉的演说家。罗博士接到AZ Medimmune的研究支持。 Dr. Laforce has received personal compensation for activities with Eli Lilly Canada Inc. as a member of the scientific advisory board. Dr. Finger has nothing to disclose. Dr. Frisoni has nothing to disclose. Dr. Mendonça has nothing to disclose. Dr. Sorbi has nothing to disclose. Dr. Gazzina has nothing to disclose. Dr. Cosseddu has nothing to disclose. Dr. Archetti has nothing to disclose. Dr. Gasparotti has nothing to disclose. Dr. Manes has nothing to disclose. Dr. Alberici has nothing to disclose. Dr. Cardoso has nothing to disclose. Dr. Bocchetta has nothing to disclose. Dr. Cash has nothing to disclose. Dr. Ourselin has nothing to disclose. Dr. Padovani has nothing to disclose. Dr. Rohrer has nothing to disclose. Dr. Borroni has nothing to disclose.
