Integrated Single-Cell Multi-Omics Analysis Reveals That a CD8+ TPex–Monocyte Interaction Axis Coordinates Immune Infiltration in Alzheimer’s Disease

Alzheimer's disease (AD) is a major public health issue, and the role of peripheral immunity in its pathogenesis remains poorly understood. This study conducted a comprehensive reanalysis of publicly available single-cell transcriptomic and chromatin accessibility datasets to investigate immune cell dynamics in AD. By integrating data from cerebrospinal fluid and peripheral blood samples, we constructed a cross-tissue immune cell atlas. Based on Monocle3 pseudotemporal trajectory analysis, we propose the hypothesis that CD8⁺ TEMRA cells in the cerebrospinal fluid may originate from blood-derived CD8⁺ TPex cells. Furthermore, cell-cell communication analysis revealed a potential interaction mechanism whereby CD8⁺ TPex cells secrete MIF signals to activate monocytes, prompting them to release increased levels of inflammatory factors (<i>IL1B</i>) and adhesion molecules (<i>ICAM1</i>). These inflammatory factors collectively contribute to the disruption of the blood-brain barrier, thereby facilitating immune cell infiltration. Our reanalysis provides a novel interpretation of existing data, establishes a regulatory framework for understanding immune infiltration in AD.