Identification of Peripheral Blood GZMK⁺ CD8⁺ T Cells As Biomarkers of Alzheimer's Disease Based on Single-Cell Transcriptome

  Objective  Based on single-cell RNA sequencing (scRNA-seq) to explore immune characteristics in the peripheral blood of patients with Alzheimer's disease (AD) as biomarkers.

  Methods  GSE168522, the scRNA-seq dataset of AD peripheral blood immune cells, was downloaded from the Gene Expression Omnibus (GEO) database and was analyzed in the RAD-Blood web server (http://www.bioinform.cn/RAD-Blood/). The changes in blood cell composition in AD patients were analyzed. The abnormal communications between different types of cells in AD patients were investigated by the CellChat R package.

  Results  There were two kinds of CD8⁺ T cells in the blood of AD patients and healthy individuals, one of which highly expressed granzyme K (GZMK) (false discovery rate FDR<0.05), and the other highly expressed GZMA, GZMB, and GZMH (FDR<0.05). In the blood of AD patients, the content of GZMK⁺ CD8⁺ T cells was increased by 32.9% (P=5.15E-21), their interactions with other cell types were increased, and they might be associated with AD through the abnormal signal transduction of major histocompatibility complex class Ⅰ (MHC-Ⅰ). Erythrocyte provided the main ligands, that are, human leukocyte antigen (HLA) class Ⅰ molecules, including HLA-A, HLA-B, HLA-C, and HLA-E, for the abnormal MHC-Ⅰ signaling pathway of GZMK⁺ CD8⁺ T cells. The RESISTIN signaling pathway was specifically enriched in the blood of AD patients.

  Conclusion  The increased content of peripheral blood GZMK⁺ CD8⁺ T cells, the increased interaction between GZMK⁺ CD8⁺ T cells and erythrocytes, and the enhanced RESISTIN pathway are potential blood biomarkers of AD.