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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

整合的基因组分析揭示了APOE4非携带者中阿尔茨海默氏病的相关基因

卷 16, 期 8, 2019

页: [753 - 763] 页: 11

弟呕挨: 10.2174/1567205016666190823124724

价格: $65

摘要

背景：APOE4是晚期阿尔茨海默氏病（LOAD）的最强遗传危险因素。携带或不携带APOE4的LOAD患者表现出明显的临床病理特征。已显示APOE4通过影响病理过程的各个方面在AD的发病机理中起关键作用。但是，涉及不携带LOAD APOE4的发病机制仍然难以捉摸。 目的：我们旨在鉴定与LOAD不携带APOE4有关的相关基因。 方法：对全基因组关联研究，全基因组表达谱和全基因组连锁扫描以及蛋白质-蛋白质相互作用网络构建的数据集进行综合基因组分析，以鉴定APOE4非携带者中的相关基因簇。通过敲除和western印迹研究了APOE4非载体相关基因簇的一个枢纽基因在tau磷酸化中的作用。 结果：我们鉴定了与AD APOE4非携带者相关的12个基因簇。在这些簇中与AD相关的中枢基因是MAPK8，POU2F1，XRCC1，PRCKG，EXOC6，VAMP4，SIRT1，MME，NOS1，ABCA1和LDLR。 APOE4非携带者的相关基因在遗传性疾病，神经疾病和心理疾病中丰富。此外，在存在APOE3而不是APOE4的情况下，敲低PRKCG以减少蛋白激酶Cγ亚型的表达可增强Thr181和Thr231处的tau磷酸化以及糖原合酶激酶3β和细胞周期蛋白依赖性激酶5的表达。 结论：该研究为不携带APOE4的LOAD的独特发病机理提供了新见解，并促进了基于APOE基因型的鉴定基因的功能探索。

关键词: 迟发性阿尔茨海默病，APOE4，APOE4非载体，整合基因组分析，蛋白激酶Cγ，tau磷酸化。

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