Objective To compare the differential genes in different stages of Braak between apolipoprotein E(ApoE)-ε4 positive and ApoE-ε4 negative Alzheimer's disease(AD)patients.To provide important targets for blocking the pathological progression of AD patients carrying ApoE-ε4.Methods Download the dataset GSE29652 from the Gene Expression Integrated Database(GEO)and use R language to identify differentially expressed genes(DEGs).Using STRING database and Cytoscape software for protein interaction network a-nalysis and screening of key target genes.Perform functional enrichment and pathway analysis of key target genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.Results A total of one thousand four hundred and seventeen differentially expressed genes related to ApoE-ε4 negative and ApoE-ε4 positive were screened for Braak Ⅰ-Ⅱ stage in AD patients.Six key target genes were obtained based on multiple al-gorithms:TNF、IL17A、CD8A、IL7R、TLR2、IL18.Among them,IL7R was significantly down regulated(P＜0.05),TLR2 and CD8A were significantly upregulated(P＜0.05).GO and KEGG analysis showed that the three target genes were mainly enriched in lymphocyte-mediated immunity,cell membrane transmis-sion,NAD+nucleosidase activity,and involved signaling pathways such as primary immunodeficiency,anti-gen processing and presentation,and PI3K-Akt signal pathway,and so on.During the Braak Ⅲ-Ⅳ stage,one thousand and fifty differentially expressed genes were screened for ApoE-ε4 negative and ApoE-ε4 posi-tive,and five key target genes were obtained based on multiple algorithms:IGF1、LEP、PTGS2、INS and PT-PN11.Among them,PTPN11 was significantly upregulated(P＜0.05).GO and KEGG analysis showed that its functional enrichment is mainly related to the ERK1 and ERK2 cascade,peptidyl-tyrosine phosphoryl-ation,regulation of hormone secretion,protein tyrosine kinase and hormone receptor binding,involving the JAK-STAT and Ras signaling pathways.In the Braak Ⅴ-Ⅵ stage,a total of three hundred and sixty-four dif-ferentially expressed genes related to ApoE-ε4 negative and ApoE-ε4 positive were screened.Based on the De-gree algorithm,twelve key target genes were obtained,among which RAC1 was significantly downregulated(P＜0.05)and MYH6 was significantly upregulated(P＜0.05).GO and KEGG analysis showed that the two target genes were mainly enriched in actin filament polymerization and calmodulin binding,involving sig-naling pathways such as cell apoptosis.Conclusion In the early stages,ApoE-ε4 mainly promotes early in-flammation by regulating TLR2、IL7R and CD8A genes.In the mid-term stage,ApoE-ε4 can lead to hormone dysfunction dependent on PTPN11 gene and accelerate AD pathology.In the late stage of AD,ApoE-ε4 may be closely related to the regulation of calcium ions by RAC1 and MYH6.
维普
万方数据
