Machine learning analysis showed that the AD classification performance (area under the curve (AUC) = 0.807) of age, sex, and <i>apoE</i> ε4 carrier status was significantly improved by 6.3% with inclusion of five AD-associated hub miRNAs.<h4>Conclusions</h4>Integrative network and machine learning analysis identified miRNA signatures, especially miR-129-5p, as associated with AD, its neuropathology markers, and cognition, enhancing our understanding of AD pathogenesis and leading to better performance of AD classification as potential diagnostic/prognostic biomarkers. This evidence concerns the gene APOE and Alzheimer disease.