M10, a 62-member module with the most significant negative correlation to AD phenotypes (Fig. 4), was highly enriched with ion-transporting ATPases, such as Na+/K+ ATPase subunits (ATP1A2, ATP1B1, and ATP1B2) for establishing the electrochemical gradients of Na and K ions across the plasma membrane and the H+-transporting, vacuolar ATPase subunit ATP6V1G2 for lysosomal acidification (Fig. 7 and Additional file 6: Table S6), supporting a loss of brain cell ion homeostasis in AD pathogenesis [20, 81]. This evidence concerns the gene ATP1B2 and Alzheimer disease.