Identification of dysregulated genes and pathways of different brain regions in Alzheimer’s disease

Abstract

Background: Alzheimer’s disease (AD) is a degenerative neurologic disease. The study aimed to identify the key differentially expressed genes (DEGs) and pathways in AD pathogenesis and obtain potential biomarkers in AD diagnosis.Methods: An integrated analysis of publicly available Gene Expression Omnibus datasets of AD was performed. DEGs in hippocampus tissue (HIP), temporal gyrus tissue (TG), frontal gyrus tissue (FG) and whole blood (WB) were identified. Bioinformatics analyses were used to insight into the functions of DEGs. The expression levels of candidate DEGs were preliminarily validated in GSE1297. The discriminatory ability of candidate DEGs in WB samples of AD patients and healthy individuals was evaluated in GSE63060 and GSE63061 datasets through receiver operating characteristic (ROC) analysis.Results: The DEGs in HIP, TG and FG tissues of AD were identified. Functions involved in regulation of apoptotic process, apoptotic process and cell death were significantly enriched from DEGs in AD. MAPK signaling pathway and Wnt signaling pathway were significantly enriched. YAP1, MAPK9 and GJA1 were the hub proteins in protein–protein interaction network in HIP, TG and FG. The expression levels of 14 DEGs in GSE1297 dataset were consistent with our integrated analysis. Moreover, 7 out of 14 DEGs had the diagnostic value in distinguishing AD patients from healthy controls in both GSE630060 and GSE630061 datasets.Conclusion: The DEGs including YAP1, MAPK1, GJA1 and pathways including MAPK signaling pathway and Wnt signaling pathway may be related to AD progression. RAD51C, SAFB2, SSH3 and TXNDC9 might be potential biomarkers in AD diagnosis.