Our research comprehensively explored 28 immune cell subsets and various immune-modulators in the AD immune microenvironment, and based on the advantages of machine learning in clinical applications, we finally identified six key immune cell subtypes (plasmacytoid dendritic cell, type 17 T helper cell, immature B cell, natural killer cell, MDSC, and neutrophil) and five vital immune genes (CXCR4, PPP3R1, HSP90AB1, CXCL10, and S100A12) that can accurately predict AD progression, some of which have never been reported in AD before. This evidence concerns the gene S100A12 and Alzheimer disease.