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To explore potential molecular mechanisms and novel biomarkers of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The mRNA expression datasets GSE63060 and GSE63061 and the miRNA expression dataset GSE120584 were obtained from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and miRNA (DEmiRs) were identified in the normal, MCI, and AD groups. Mfuzz clustering and weighted correlation network analyses (WGCNA) were conducted, followed by pathway and functional enrichment analyses and miRNA-mRNA network construction. Furthermore, phenotypic correlation analysis and experimental verification were performed on key DEGs and DEmiRs. In total, 3,000 intersected DEGs from GSE63060/GSE63061 and 817 DEmiRs from GSE120584 were obtained. Mfuzz and WGCNA analyses revealed 106 DEGs including ribosomal protein L11 ( RPL11 ) and 28 DEmiRs including miR-6764-5p. These DEGs and DEmiRs were mainly enriched in pathways like Ribosome. Moreover, 5 key DEGs including cytohesin 4 ( CYTH4 ) and 6 crucial DEmiRs including miR-6734-3p were identified by miRNA–mRNA interaction network analysis. Phenotypic correlation analysis showed that  CYTH4  and miR-6734-3p were correlated with patients’ age. The results of quantitative polymerase chain reaction analysis confirmed that  RPL11  expression was significantly downregulated in the MCI and AD groups compared to that in the normal group, while the expression of  CYTH4 , miR-6764-5p, and miR-6734-3p was remarkably upregulated in the MCI and AD groups. miR-6764-5p might contribute to MCI and AD by targeting  RPL11  in the ribosome pathway. Therefore, miR-6734-3p and its target mRNA  CYTH4  might be used as novel biomarkers for MCI and AD.

Usefulness of candidate mRNAs and miRNAs as biomarkers for mild cognitive impairment and Alzheimer’s disease