Exploring shared genetic signatures of Alzheimer’s disease and multiple sclerosis: a bioinformatic analysis study

Many clinical studies reported the coexistence of Alzheimer's disease (AD) and multiple sclerosis (MS), but the common molecular signature between AD and MS remains elusive. The purpose of our study is to explore the genetic linkage between AD and MS through bioinformatic analysis, providing new insights into the shared signatures and possible pathogenesis of two diseases.The common differential expressed genes (DEGs) were determined between AD and MS from datasets obtained from Gene Expression Omnibus (GEO) database. Further, functional and pathway enrichment analysis, PPI network construction, and identification of hub genes were carried out. The expression level of hub genes was validated in two other external AD and MS datasets. Transcription factor (TF)-gene interactions and gene-miRNA interactions were performed in NetworkAnalyst. Finally, receiver operating characteristic (ROC) curve analysis was applied to evaluate the predictive value of hub genes.A total of 75 common DEGs were identified between AD and MS. Functional and pathway enrichment analysis emphasized the importance of exocytosis and synaptic vesicle cycle, respectively. Six significant hub genes, including CCL2, CD44, GFAP, NEFM, STXBP1, and TCEAL6 were identified and verified as common hub genes shared by AD and MS. FOXC1 and hsa-mir-16-5p are the most common TF and miRNA in regulating hub genes, respectively. In the ROC curve analysis, all hub genes showed good efficiency in helping distinguishing patients from controls.Our study firstly identified a common genetic signature between AD and MS, paving the road for investigating shared machanism of AD and MS.