Shared Molecular Mechanisms between Alzheimer’s Disease and Periodontitis Revealed by Transcriptomic Analysis

Abstract

Objective. To investigate the genetic crosstalk mechanisms that link periodontitis and Alzheimer’s disease (AD). Background. Periodontitis, a common oral infectious disease, is associated with Alzheimer’s disease (AD) and considered a putative contributory factor to its progression. However, a comprehensive investigation of potential shared genetic mechanisms between these diseases has not yet been reported. Methods. Gene expression datasets related to periodontitis were downloaded from the Gene Expression Omnibus (GEO) database, and differential expression analysis was performed to identify differentially expressed genes (DEGs). Genes associated with AD were downloaded from the DisGeNET database. Overlapping genes among the DEGs in periodontitis and the AD-related genes were defined as crosstalk genes between periodontitis and AD. The Boruta algorithm was applied to perform feature selection from these crosstalk genes, and representative crosstalk genes were thus obtained. In addition, a support vector machine (SVM) model was constructed by using the scikit-learn algorithm in Python. Next, the crosstalk gene-TF network and crosstalk gene-DEP (differentially expressed pathway) network were each constructed. As a final step, shared genes among the crosstalk genes and periodontitis-related genes in DisGeNET were identified and denoted as the core crosstalk genes. Results. Four datasets (GSE23586, GSE16134, GSE10334, and GSE79705) pertaining to periodontitis were included in the analysis. A total of 48 representative crosstalk genes were identified by using the Boruta algorithm. Three TFs (FOS, MEF2C, and USF2) and several pathways (i.e., JAK-STAT, MAPK, NF-kappa B, and natural killer cell-mediated cytotoxicity) were identified as regulators of these crosstalk genes. Among these 48 crosstalk genes and the chronic periodontitis-related genes in DisGeNET, C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3 were shared and identified as the most pivotal candidate links between periodontitis and AD. Conclusions. Exploration of available transcriptomic datasets revealed C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3 as the top candidate molecular linkage genes between periodontitis and AD.

Gene Differential Expression and Interaction Networks Illustrate the Biomarkers and Molecular Mechanisms of Atherosclerotic Cerebral Infarction

“…FCGR3A is also named as CD16 which has been identified as the pathogenic factor to participate in the deterioration of atherosclerosis, and the study has indicated that FCGR3A may be connected with ischemic stroke [ 12 , 28 ]. Besides, several studies have shown that both FCGR3A and MAPK pathway exhibited significant aberrant levels in some diseases such as chronic constriction and Periodontitis [ 29 , 30 ], while few studies have indicated the connection of FCGR3A and MAPK pathway.…”

Similarity and Potential Relation Between Periimplantitis and Rheumatoid Arthritis on Transcriptomic Level: Results of a Bioinformatics Study

“…This is the first analysis of cross-talk mechanisms between periimplantitis and RA on the transcriptomic level. Bioinformatics analysis has been applied for several other diseases and conditions, such as periodontitis and Alzheimer’s disease, periodontitis and oral cancer, or between periimplantitis and type 2 diabetes mellitus ( 20 , 21 , 53 ). Therefore, this method appears reasonable for the current study aim, i.e., detecting the cross-talk between periimplantitis and RA to reveal whether there is a similarity regarding auto-inflammation between the two diseases.…”

“…Recently, the molecular mechanism, including genetics and epigenetics between oral and systemic diseases, has been successfully explored by bioinformatics analysis. So an interlink between periodontitis and Alzheimer’s disease, or between periimplantitis and type 2 diabetes mellitus, has been detected ( 20 , 21 ). Accordingly, this current study used bioinformatics to reveal the cross-talk mechanisms between periimplantitis and RA at the transcriptomic level.…”

Identification of Neuropeptides as Potential Crosstalks Linking Down Syndrome and Periodontitis Revealed by Transcriptomic Analyses

“…The combination of crosstalk genes, neuropeptides, and pathways was very comprehensive and is up until now unique in literature. Other working groups [ 31 , 32 ] have already successfully applied similar methodology previously to reveal the link between periodontal and systemic diseases. However, several limitations exist.…”