CR2 and Alzheimer disease: 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.