国际老年医学杂志2024，Vol.45Issue(4)：390-396,7.DOI:10.3969/j.issn.1674-7593.2024.04.002
单细胞组学揭示免疫补体系统抑制作为牙周炎与阿尔茨海默病的共同病理机制
Single-cell Genomics Revealed Immunocomplement System Suppression as a Shared Pathogenic Cause of Periodontitis and Alzheimer's Disease
摘要
Abstract
Objective Periodontitis and Alzheimer's disease are prevalent among the elderly,with an incidence that increa-ses 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 i-dentified by comparing the gene expression profiles.Enrichment analysis of these shared genes was conducted,followed by the con-struction of a protein-protein interaction(PPI)network to understand the interactions between proteins.Bulk RNA-seq microarray ex-pression matrices and sample information for PD(GSE16134)and AD(GSE63060)were downloaded from the GEO database to vali-date the expression levels of core genes in the PPI network from the single-cell data and to assess the correlation between genes and dis-eases.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 com-mon 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.关键词
牙周炎/阿尔茨海默病/免疫反应/髓系细胞/补体Key words
Periodontitis/Alzheimer's disease/Immune response/Myeloid cells/Complement引用本文复制引用
孙天萌,孙泽文,赵天元,徐梦钰,孙宏晨,安政雯..单细胞组学揭示免疫补体系统抑制作为牙周炎与阿尔茨海默病的共同病理机制[J].国际老年医学杂志,2024,45(4):390-396,7.基金项目
科技部"十四五"国家重点研发计划重点专项(2022YFC2504200) （2022YFC2504200）
国家自然科学基金面上项目(82270960) （82270960）
吉林省财政厅科技项目(JCSZ2021893-35) （JCSZ2021893-35）
