Assessments of neuronal insulin signaling at its first node, insulin receptor substrate-1 (IRS-1), and along the canonical (AKT, GSK-3β, and p70S6K) and alternative (ERK1/2, JNK, and p38-MAPK) pathways showed that NDEV biomarkers of the insulin signaling pathway were associated with cognitive dysfunction and brain structural abnormalities in patients with BD [41]. This evidence concerns the gene INS and Behcet disease.