Analysis Of Immune Characteristics At Single Cell Level In Patients With Alzheimer’s Disease

Objectives:The aim of this study was to integrate single cell RNA sequencing（sc RNA-seq）data from multiple databases to analyze the characteristics of peripheral and central immune cell alteration in patients with Alzheimer’s disease（AD）,and thus to reveal the underlying neuroinflammatory mechanism of AD.Methods:Two datasets,GSE181279 and GSE134578 were selected from GEO database.Based on single cell RNA sequencing,GSE181279 measured the PBMC cells of AD patients,and GSE134578 measured the CD8⁺T cells in AD patients’peripheral blood and the CD45⁺immune cells in cerebrospinal fluid（CSF）.Seurat and other packages were used for quality control of these two datasets,followed by linear dimension reduction clustering,marker gene identification,peripheral immune cell subsets analysis,peripheral immune cell subsets proportion identification,peripheral T cell subsets proportion identification and CSF CD8+T cell clustering.Above analysis can describe the alteration of immune cells in AD patients,especially the state of T cells,searching for the potential mechanisms of the pathogenesis of AD.Results:The proportion of T cells in peripheral blood of AD patients was significantly expanded,and the mainly expansion subpopulation of T cells was CD8⁺_TEMRA、CD4⁺_TEMRAand CD8⁺_TEMcells.In addition,T cells in AD patients were mainly effector T cells,while in NC,T cells were mainly in the resting state,such as CD4⁺_TCM,CD4⁺Na（?）ve,CD8⁺_TCMcells.Monocle analysis suggested that CD4⁺_TEMRA cells were developed from CD4⁺Na（?）ve and CD4⁺_TCMcells,while CD4⁺_TEM cells were in the intermediate state of this developing process.CD8⁺T cells follow the same developmental trajectory.In cerebrospinal fluid of AD patients,analysis of single-cell TCR sequencing data showed that the amplified T cells were mainly CD8⁺_TEMRA cells.Compared with NC,the number and intensity of communication between CD4⁺_TEM,CD4⁺_TCM,CD8⁺_TEM cells and CD8⁺_TEMRA cells were decreased in AD patients.Conclusions:1.In AD patients,T cells were significantly expanded,and these T cells were possessed effector function,such as CD8⁺_TEMRA、CD4⁺_TEMRAand CD8⁺_TEM.2.CD8⁺_TEMRA and CD4⁺_TEMRAcells were clustered and grouped into two subsets adjacent to each other,suggesting that these two cell subpopulations may have similar biological functions.3.CD4⁺_TEMRA were developed from CD4+Na（?）ve cells and CD4⁺_TCM,while CD4⁺_TEMwere in the intermediate state of this developing process.Similarly,CD8⁺T cells follow the same developmental trajectory.4.In cerebrospinal fluid of AD patients,the amplified T cells were mainly CD8⁺_TEMRAcells.And the number and intensity of communication between CD4⁺_TEM,CD4⁺_TCM,CD8⁺_TEMand CD8⁺_TEMRA were decreased in AD patients.