Identification of key genes and pathways for Alzheimer's disease via combined analysis of genome-wide expression profiling in the hippocampus

• 作者: Jing Wang Kechi Fang Liyuan Guo Mengsi Wu Wei Lin Weixiao Wang
• 来源期刊: 生物物理学报:英文版
• 学科: 生物学
• 关键词: Alzheimer's disease Combined analysis HIPPOCAMPUS Gene expression DIFFERENTIALLY EXPRESSED genes MICROARRAY
• 年，卷（期）: 2019,（2）
• 页码范围: 98-109
• 页数: 12页
• 分类号: Q

摘要

In this study, combined analysis of expression profiling in the hippocampus of 76 patients with Alzheimer's disease (AD) and 40 healthy controls was performed. The effects of covariates (including age, gender, postmortem interval, and batch effect) were controlled, and differentially expressed genes (DEGs) were identified using a linear mixed-effects model. To explore the biological processes, functional pathway enrichment and protein-protein interaction (PPI) network analyses were performed on the DEGs. The extended genes w让h PPI to the DEGs were obtained. Finally, the DEGs and the extended genes were ranked using the convergent functional genomics method. Eighty DEGs with q < 0.1, in eluding 67 downregulated and 13 upregulated genes, were identified. In the pathway enrichment analysis, the 80 DEGs were significantly enriched in one Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, GABAergic synapses, and 22 Gene Ontology terms. These genes were mainly involved in neuron, synaptic signaling and transmission, and vesicle metabolism. These processes are all linked to the pathological features of AD, dem on strating that the GABAergic system, neurons, and synaptic function might be affected in AD. In the PPI network, 180 extended genes were obtained, and the hub gene occupied in the most central position was CDC42. After prioritizing the candidate genes, 12 genes, including five DEGs (ITGB5, RPH3A, GNAS, THY1, and SEPT6) and seven extended genes (JUN, GDl1, GN Al2, NEK6, UBE2D3, CDC42EP4, and ERCC3), were found highly relevant to the progression of AD and recog nized as promising biomarkers for its early diag no sis.