Infusion of peripheral blood mononuclear cells alleviates amyloid accumulation and cognitive deficits in Alzheimer’s disease

Abstract Recently, the role of peripheral blood mononuclear cells (PBMCs) in neurodegenerative activities has garnered significant attention, yet the role in Alzheimer’s disease (AD) remains unclear. Based on our previous single-cell RNA sequencing data sets of PBMCs from healthy controls and AD patients, we identified differentially expressed genes (DEGs) between healthy individuals and AD patients. These DEGs are involved in pathways related to apoptosis regulation, cognition, synaptic organization, and other AD pathology-associated biological processes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. JUN, CHCHD10, HSPA8, RETN, S100A8, ITGA2B, HBG2, PPBP, and HLA-DQA2 have high correlation with these pathways. To further investigate the role of PBMCs in AD, PBMCs from 9- or 6-month-old wild-type mice were, respectively, injected into 9- or 6-month-old AD mice; we found that PBMCs could reduce Aβ plaques and phosphor-tau deposition and improve cognitive function in AD mice without side effects. Additionally, intersection analysis with AD pathogenic genes, quantitative real-time polymerase chain reaction validation, and receiver operating characteristic curves demonstrated increased JUN expression in PBMCs of AD patients with higher specificity in the diagnosis of AD, with no significant sex- and age-dependent differences observed in its expression. This study provides a critical theoretical foundation for the clinical application of PBMCs and identifies JUN as a key regulatory gene within PBMCs.