Bioinformatics-Based Analysis of Circadian Rhythm Regulation Mechanisms in Alzheimer’s Disease

BACKGROUND: There is a close association between Alzheimer’s disease (AD) and circadian rhythms, and neuroinflammatory-related pathways are associated with both interactions. OBJECTIVE: To reveal the relationship between circadian rhythm (CR) and AD at the level of genes, pathways, and molecular functions through bioinformatics. METHODS: We analyzed the differential genes between AD and control groups in GSE122063 and found the important gene modules; obtained CR-related genes from GeenCard database; used Venn 2.1 database to obtain the intersection of genes of AD important modules with CR-related genes; and used STRING database and Cytoscape 3.7.1 to construct the gene protein-protein interaction network. The MCODE plugin was used to screen pivotal genes and analyze their differential expression. We trranslated with www.DeepL.com/Translator (free version) to obtain transcriptional regulatory relationships from the TRRUST database and construct a hub gene-transcription factor relationship network. RESULTS: A total of 42 common genes were screened from AD and CR genes, mainly involving signaling pathways such as neuroactive ligand-receptor interactions. A total of 10 pivotal genes were screened from the common genes of CR and AD, which were statistically significant in the comparison of AD and control groups (p < 0.001), and ROC analysis showed that all these pivotal genes had good diagnostic significance. A total of 36 TFs of pivotal genes were obtained. CONCLUSION: We identified AD- and CR-related signaling pathways and 10 hub genes and found strong associations between these related genes and biological processes such as inflammation.