Integrated analysis of miRNA and mRNA expression in the blood of patients with Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease, which is considered the most common type of dementia worldwide. The aim of the present study was to identify key microRNAs (miRNAs/miRs) and mRNAs affecting the pathogenesis of AD, which may be developed as promising biomarkers for the early diagnosis or targeted therapy of patients with AD. Integrative analysis was performed on 12 representative miRNA datasets and three mRNA datasets of the blood from patients with AD, in order to identify differentially expressed (DE)miRNAs and DEmRNAs. Subsequently, the miRWalk database was used to identify the potential miRNA-mRNA interactions among DEmiRNAs and DEmRNAs, and an AD-specific miRNA-mRNA network was constructed using Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to assess the target mRNAs of DEmiRNAs. A total of 37 DEmiRNAs and 2,011 DEmRNAs were identified between AD and normal control samples. In addition, 853 high confidence miRNA-mRNA interactions were identified and subsequently used to construct the AD specific miRNA-mRNA network. A total of five miRNAs, including hsa-miR-93, hsa-miR-26b, hsa-miR-34a, hsa-miR-98-5p and hsa-miR-15b-5p were identified as the key nodes in the miRNA-mRNA network by topological analysis. Functional enrichment analysis demonstrated that the target mRNAs of DEmiRNAs were enriched in AD-associated pathways, such as the 'neurotrophin signaling pathway' and 'insulin signaling pathway'. Taken together, the results of the present study provide novel insights into the molecular mechanisms underlying AD and contribute to the identification of biomarkers and novel strategies for drug design for AD treatment.