生物信息学数据库中阿尔茨海默病颞叶基因表达谱相关研究

Gene Expression Profile of Temporal Lobe in Alzheimer’s Disease Based in Bioinformatics Database

目的:使用生物信息学数据库,对阿尔茨海默病(Alzheimer disease,AD)患者颞叶组织的基因表达谱进行研究,寻找与AD认知功能下降有关的发病机制。方法:使用Gene Expression Omnibus(GEO)数据库,以"Alzheimer disease""Temporal lobe""cognitive function"作为关键词进行检索,限定组织标本来自人类(Homo sapiens),检测方法为表达谱芯片(Expression profiling by array),获取2019年12月1日之前GEO数据库中的全部生物信息数据。利用ImaGEO(Integrative Gene Expression Meta-Analysis from GEO database)以及Metascape(http://metascape.org/)在线工具进行数据分析。结果:获得2个符合检索条件的数据集,共计162个样本(AD组51个,健康对照组111个)。与正常对照组人群相比,AD组患者颞叶组织中的基因有130个表达存在差异,其中有48个基因表达增多,另外82个基因表达降低,差异基因主要在细胞分泌调控、化学突触传递、蛋白质合成、离子通道调节等途径富集。差异基因中最主要的分子复合体是CASR、CCK、MCHR1和CHRM1,它们参与了和AD发生有关的蛋白激酶(PKA)、环磷腺苷结合蛋白(CREB)及γ-氨基丁酸能等神经递质的生物合成,影响着多条信号通路表达,最终导致AD患者出现认知障碍。结论:AD患者颞叶表达的差异基因参与了AD认知功能障碍发生,为进一步研究AD认知功能障碍产生相关机制提供理论基础。

Objective To analyze the gene expression profile of temporal lobe in patients with Alzheimer’s disease(AD) by bioinformatics, and to explore the mechanism related to the cognitive decline of AD. Methods "Alzheimer disease" "Temporal lobe" "cognitive function" were used to search from Gene Expression Omnibus(GEO)database, and the tissue source was defined as human(Homo sapiens). The detection method was expression profiling by array. All biological information data in GEO database before December 1 st 2019 were obtained. Use imageo(integrated gene expression meta analysis from geo database) and metascape(http://metascape.org/) online tools for data analysis. Results according to the retrieval conditions, two data sets were obtained, a total of162 samples(51 in AD group and 111 in healthy control group). Compared with the healthy control group, there were 130 gene expression differences in the temporal lobe of AD group, 48 gene expression levels increased, 82 gene expression levels decreased. Differentially expressed genes are mainly enriched in cell secretion regulation,chemical synaptic transmission, protein synthesis and ion channel regulation. CASR, CCK, MCHR1 and CHRM1 are the most important molecular complexes in the differential genes. They are involved in the biosynthesis of protein kinase(PKA), cyclic adenosine binding protein(CREB) and γ-aminobutyric acid(GABA) neurotransmitters, which are related to the occurrence of AD. they affect the expression of multiple signaling pathways and eventually lead to cognitive impairment in AD patients. Conclusion the gene expression of temporal lobe in AD patients is related to the occurrence of AD cognitive dysfunction. This study provides a theoretical basis for further understanding the mechanism of AD cognitive impairment.