Single-cell Genomics Revealed Immunocomplement System Suppression as a Shared Pathogenic Cause of Periodontitis and Alzheimer’s Disease

Abstract

Objective Periodontitis and Alzheimer’s disease are prevalent among the elderly, with an incidence that increases with age. To investigate the potential common pathogenic factors between the two diseases and provide a theoretical basis for the early diagnosis of Alzheimer’s disease, the study analyzed the pathogenic risk correlation between periodontitis and Alzheimer’s disease using single-cell transcriptomics data and Bulk RNA-seq sequencing data. Methods Single-cell data for PD (GSE164241) and AD (GSE157827) were downloaded from the Gene Expression Omnibus (GEO) database, including samples from 3 patients and 3 controls for each condition. The single-cell data were subjected to quality control, data integration, dimensionality reduction clustering, cell type annotation, and differential gene expression identification. Shared differentially expressed genes between the two diseases were identified by comparing the gene expression profiles. Enrichment analysis of these shared genes was conducted, followed by the construction of a protein-protein interaction (PPI) network to understand the interactions between proteins. Bulk RNA-seq microarray expression matrices and sample information for PD (GSE16134) and AD (GSE63060) were downloaded from the GEO database to validate the expression levels of core genes in the PPI network from the single-cell data and to assess the correlation between genes and diseases. Results Comparative analysis of sample data from periodontitis and Alzheimer’s disease revealed CD163+ myeloid cells as a common immune cell type in both conditions. In periodontitis-derived myeloid cells, 1934 downregulated differentially expressed genes were found in the disease group compared to the control group, while in Alzheimer’s disease-derived myeloid cells, 232 downregulated genes were identified, with an intersection of 49 shared downregulated genes. Enrichment analysis of these genes primarily highlighted myeloid cell and complement system-related responses. Further analysis showed that the expression of STAB1 gene in the complement system was significantly negatively correlated with both periodontitis and Alzheimer’s disease. Conclusion Myeloid cells are a common immune cell type in both periodontitis and Alzheimer’s disease. STAB1 acts as a downstream target of complement pathway closely related to both diseases and shows a significant negative correlation with disease onset. This suggests that the detection of STAB1 gene expression levels in periodontitis patients could serve as potential targets for the early diagnosis and treatment of Alzheimer’s disease.

Keywords

• periodontitis
• alzheimer’s disease
• immune response
• myeloid cells;complement