Common miRNAs, Genes, and Regulatory Pathways in Alzheimer's Disease and Type 2 Diabetes Mellitus: An Integrative Analysis of Systematic Reviews, Bioinformatics and Data Mining

Abstract

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are frequent conditions affecting older adults, with evidence suggesting a higher predisposition for AD in diabetic patients. MicroRNAs (miRNAs) are proposed as regulators of gene expression in the mutual pathways among these diseases. This study aimed to investigate circulating miRNAs found to be expressed both in AD and T2DM, as well as their target genes and associated molecular pathways, using systematic reviews (SRs), bioinformatics analyses, and data mining. Two independent SRs were conducted to identify differentially expressed miRNAs in AD and T2DM compared to their respective controls. Searches covered major databases (EMBASE, PubMed, Cochrane, Scopus, Cinahl, Web of Science), gray literature, and reference lists, following the Joanna Briggs Institute (JBI) and PRISMA guidelines. Results were combined to identify miRNAs shared by both AD and T2DM, with target genes extracted from miRTarBase. Pathway enrichment analysis was performed using EnrichR, and relevant pathways were ranked based on gene involvement frequency with artificial intelligence tools. From the SRs (AD: 49 studies; T2DM: 104 studies), 21 miRNAs were identified as commonly expressed (10 upregulated, and 11 downregulated). 337 and 233 genes are potential targets for these down- and upregulated miRNAs, respectively. The key pathways identified from those genes were the TCR-RAS signaling cascade for downregulated miRNAs and the extracellular matrix pathway for upregulated miRNAs. Our findings highlight shared biological pathways between AD and T2DM and provide insights into their shared pathophysiology and potential therapeutic targets.