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 (IL1B) and adhesion molecules (ICAM1). 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.