In particular, protein kinases IKBKB, AKT1, CDK5, CSK, MAPK3, PRKCZ and RAF1, whose substrates were enriched in at least three brain regions’ perturbed subnetworks, were also hub genes, suggesting that they may play vital roles in the regulation of signal transduction and tau phosphorylation in AD. The gene discussed is RAF1; the disease is Alzheimer disease.