Alzheimer’s disease and type 2 diabetes mellitus: common mirnas, genes and regulatory biological pathways

Background: The increased incidence of Type 2 Diabetes Mellitus (T2DM) in the 21st century, along with the higher risk of developing Alzheimer’s disease (AD) in diabetic patients have stimulated the search for pathways that link glycemic disorders to neurodegeneration. MicroRNAs (miRNAs) are non-coding RNAs that play key roles in regulating gene expression. Objective: To identify miRNAs, genes and their regulatory pathways in common in AD and T2DM. Methods: Literature search was carried out to find miRNAs commonly expressed in AD and T2DM. MiRTarBase database was used to provide experimentally validated information on the interactions between miRNAs and their target genes. The functional enrichment of molecular pathways differentially regulated by these miRNAs was performed using EnrichR with Reactome gene set annotation. Results: We found six circulating miRNAs commonly expressed in both diseases (hsa-mir-21; hsamir-103a-1; hsa-mir-103a-2; hsa-mir-107; hsa-mir-146a and hsa-mir-144), which regulate 129 target genes. The common pathways between AD and T2DM were related to inflammatory mediators, cell death and axon formation signalling with p-adjust <10-5. Conclusion: Our study provides evidence that AD and T2DM share common pathophysiological mechanisms and regulators miRNAs, and suggests miRNAs as potential markers related to both diseases.