Imagine a bustling city with two major highways running side by side. The first highway represents Alzheimer’s Disease (AD), while the second one symbolizes Type 2 Diabetes Mellitus (DM). In this study, scientists embarked on a journey to explore the intricate network of roads where these two highways intersect. By analyzing gene expression data and using advanced algorithms, they uncovered 339 common genes that play a crucial role in both AD and DM. They discovered that immunity, hormones, cytokines, neurotransmitters, and insulin are key players in these diseases, highlighting their importance in their shared pathophysiological mechanisms. Just like various exits on a highway lead to different destinations, specific biological pathways such as serotonergic synapse, ovarian steroidogenesis, estrogen signaling, and regulation of lipolysis were found to be closely related to both AD and DM. Furthermore, the researchers utilized computational tools to identify potential drugs that could reverse the pathological functions of AD and DM. They also pinpointed 10 hub genes, including PTGS2, RAB10, LRRK2, SOS1, EEA1, NF1, RAB14, ADCY5, RAPGEF3, and PRKACG, which hold promise for future investigations into the mechanisms and treatments of these complex diseases. This study not only provides important insights into the common pathways between AD and DM but also opens new avenues for further research in understanding and combating these conditions.

BackgroundAlzheimer’s Disease (AD) and Type 2 Diabetes Mellitus (DM) have an increased incidence in modern society. Although more and more evidence has supported that DM is prone to AD, the interrelational mechanisms remain fully elucidated.PurposeThe primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and DM.MethodsDownload the expression matrix of AD and DM from the Gene Expression Omnibus (GEO) database with sequence numbers GSE97760 and GSE95849, respectively. The common differentially expressed genes (DEGs) were identified by limma package analysis. Then we analyzed the six kinds of module analysis: gene functional annotation, protein–protein interaction (PPI) network, potential drug screening, immune cell infiltration, hub genes identification and validation, and prediction of transcription factors (TFs).ResultsThe subsequent analyses included 339 common DEGs, and the importance of immunity, hormone, cytokines, neurotransmitters, and insulin in these diseases was underscored by functional analysis. In addition, serotonergic synapse, ovarian steroidogenesis, estrogen signaling pathway, and regulation of lipolysis are closely related to both. DEGs were input into the CMap database to screen small molecule compounds with the potential to reverse AD and DM pathological functions. L-690488, exemestane, and BMS-345541 ranked top three among the screened small molecule compounds. Finally, 10 essential hub genes were identified using cytoHubba, including PTGS2, RAB10, LRRK2, SOS1, EEA1, NF1, RAB14, ADCY5, RAPGEF3, and PRKACG. For the characteristic Aβ and Tau pathology of AD, RAPGEF3 was associated significantly positively with AD and NF1 significantly negatively with AD. In addition, we also found ADCY5 and NF1 significant correlations with DM phenotypes. Other datasets verified that NF1, RAB14, ADCY5, and RAPGEF3 could be used as key markers of DM complicated with AD. Meanwhile, the immune cell infiltration score reflects the different cellular immune microenvironments of the two diseases.ConclusionThe common pathogenesis of AD and DM was revealed in our research. These common pathways and hub genes directions for further exploration of the pathogenesis or treatment of these two diseases.

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