Machine-learning models based on differentially expressed genes and proteins accurately classified AD age groups (transcript-based F1 = 0.70, AUC = 0.79), identifying stable markers such as <i>IRF2</i> , <i>PDK4</i> , <i>ZFP90</i> , CD21, CD94, and CD122.<h4>Conclusions</h4>Single-cell multi-omics profiling revealed immune differences across the AD lifespan, transitioning from developmental tolerance in children to inflammatory and metabolic activation in adults to enhanced innate signaling in geriatric individuals. Here, PDK4 is linked to Alzheimer disease.