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Integrated Genomic Analysis Revealed Associated Genes for Alzheimer's Disease in APOE4 Non-Carriers 期刊论文

编号：

9b775b08-647b-4e6c-b602-791f19b7e3b1
作者：

Jiang, Shan#^[1,3]Zhang, ChunYun#^[1]Tang, Ling#^[1]Zho, LanXue^[1];Chen, HongZhuan*^[2]Qiu, Yu*^[1]
语种：

英文
期刊：

CURRENT ALZHEIMER RESEARCH ISSN：1567-2050 2019 年 16 卷 8 期 (753 - 763)
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关键词：

late-onset Alzheimer's disease APOE4 APOE4 non-carriers integrated genomic analysis protein kinase C-gamma tau phosphorylation
摘要：

Background: APOE4 is the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD). LOAD patients carrying or not carrying APOE4 manifest distinct clinico-pathological characteristics. APOE4 has been shown to play a critical role in the pathogenesis of AD by affecting various aspects of pathological processes. However, the pathogenesis involved in LOAD not-carrying APOE4 remains elusive.
Objective: We aimed to identify the associated genes involved in LOAD not-carrying APOE4.
Methods: An integrated genomic analysis of datasets of genome-wide association study, genome-wide expression profiling and genome-wide linkage scan and protein-protein interaction network construction were applied to identify associated gene clusters in APOE4 non-carriers. The role of one of hub gene of an APOE4 non-carrier-associated gene cluster in tau phosphorylation was studied by knockdown and western blot.
Results: We identified 12 gene clusters associated with AD APOE4 non-carriers. The hub genes associated with AD in these clusters were MAPK8, POU2F1, XRCC1, PRKCG, EXOC6, VAMP4, SIRT1, MME, NOS1, ABCA1 and LDLR. The associated genes for APOE4 non-carriers were enriched in hereditary disorder, neurological disease and psychological disorders. Moreover, knockdown of PRKCG to reduce the expression of protein kinase C gamma isoform enhanced tau phosphorylation at Thr181 and Thr231 and the expression of glycogen synthase kinase 3 beta and cyclin-dependent kinase 5 in the presence of APOE3 but not APOE4.
Conclusion: The study provides new insight into the mechanism of distinct pathogenesis of LOAD not carrying APOE4 and prompts the functional exploration of identified genes based on APOE genotypes.
推荐引用方式
GB/T 7714：

Jiang Shan,Zhang Chun-Yun,Tang Ling, et al. Integrated Genomic Analysis Revealed Associated Genes for Alzheimer's Disease in APOE4 Non-Carriers [J].CURRENT ALZHEIMER RESEARCH,2019,16(8):753-763.
APA：

Jiang Shan,Zhang Chun-Yun,Tang Ling,Zho Lan-Xue,&Qiu Yu.(2019).Integrated Genomic Analysis Revealed Associated Genes for Alzheimer's Disease in APOE4 Non-Carriers .CURRENT ALZHEIMER RESEARCH,16(8):753-763.
MLA：

Jiang Shan, et al. "Integrated Genomic Analysis Revealed Associated Genes for Alzheimer's Disease in APOE4 Non-Carriers" .CURRENT ALZHEIMER RESEARCH 16,8(2019):753-763.
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