Bioinformatic prediction of the molecular links between Alzheimer's disease and diabetes mellitus.

ABSTRACT

Background: Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2) are chronic degenerative diseases with complex molecular processes that are potentially interconnected. The aim of this work was to predict the potential molecular links between AD and DM2 from different sources of biological information. Materials and Methods: In this work, data mining of nine databases (DisGeNET, Ensembl, OMIM, Protein Data Bank, The Human Protein Atlas, UniProt, Gene Expression Omnibus, Human Cell Atlas, and PubMed) was performed to identify gene and protein information that was shared in AD and DM2. Next, the information was mapped to human protein-protein interaction (PPI) networks based on experimental data using the STRING web platform. Then, gene ontology biological process (GOBP) and pathway analyses with EnrichR showed its specific and shared biological process and pathway deregulations. Finally, potential biomarkers and drug targets were predicted with the Metascape platform. Results: A total of 1,551 genes shared in AD and DM2 were identified. The highest average degree of nodes within the PPI was for DM2 (average = 2.97), followed by AD (average degree = 2.35). GOBP for AD was related to specific transcriptional and translation genetic terms occurring in neurons cells. The GOBP and pathway information for the association AD-DM2 were linked mainly to bioenergetics and cytokine signaling. Within the AD-DM2 association, 10 hub proteins were identified, seven of which were predicted to be present in plasma and exhibit pharmacological interaction with monoclonal antibodies in use, anticancer drugs, and flavonoid derivatives. Conclusion: Our data mining and analysis strategy showed that there are a plenty of biological information based on experiments that links AD and DM2, which could provide a rational guide to design further diagnosis and treatment for AD and DM2.