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.