Exploring the Key Genes and Identification of Potential Diagnosis Biomarkers in Alzheimer's Disease Using Bioinformatics Analysis

作者全名："Yu, Wuhan; Yu, Weihua; Yang, Yan; Lu, Yang"

作者地址："[Yu, Wuhan; Lu, Yang] Chongqing Med Univ, Dept Geriatr, Affiliated Hosp 1, Chongqing, Peoples R China; [Yu, Weihua] Chongqing Med Univ, Inst Neurosci, Chongqing, Peoples R China; [Yang, Yan] Chongqing Univ, Coll Elect Engn, State Key Lab Power Transmiss Equipment & Syst Se, Chongqing, Peoples R China"

通信作者："Lu, Y (corresponding author), Chongqing Med Univ, Dept Geriatr, Affiliated Hosp 1, Chongqing, Peoples R China."

来源：FRONTIERS IN AGING NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000667225300001

JCR分区：Q2

影响因子：4.8

年份：2021

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Alzheimer's disease; diagnosis biomarkers; hub genes; integrative analysis; aging

摘要："Background Alzheimer's disease (AD) is one of the major threats of the twenty-first century and lacks available therapy. Identification of novel molecular markers for diagnosis and treatment of AD is urgently demanded, and genetic biomarkers show potential prospects. Method We identify and intersected differentially expressed genes (DEGs) from five microarray datasets to detect consensus DEGs. Based on these DEGs, we conducted Gene Ontology (GO), performed the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, constructed a protein-protein interaction (PPI) network, and utilized Cytoscape to identify hub genes. The least absolute shrinkage and selection operator (LASSO) logistic regression was applied to identify potential diagnostic biomarkers. Gene set enrichment analysis (GSEA) was performed to investigate the biological functions of the key genes. Result We identified 608 consensus DEGs, several dysregulated pathways, and 18 hub genes. Sixteen hub genes dysregulated as AD progressed. The diagnostic model of 35 genes was constructed, which has a high area under the curve (AUC) value in both the validation dataset and combined dataset (AUC = 0.992 and AUC = 0.985, respectively). The model can also differentiate mild cognitive impairment and AD patients from controls in two blood datasets. Brain-derived neurotrophic factor (BDNF) and WW domain-containing transcription regulator protein 1 (WWTR1), which are associated with the Braak stage, A beta 42 levels, and beta-secretase activity, were identified as critical genes of AD. Conclusion Our study identified 16 hub genes correlated to the neuropathological stage and 35 potential biomarkers for the diagnosis of AD. WWTR1 were identified as candidate genes for future studies. This study deepens our understanding of the transcriptomic and functional features and provides new potential diagnostic biomarkers and therapeutic targets for AD."

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