Fig. (3) Insulin/IGF1 signalling pathways and AD. Insulin or IGF1 binds with its respective specific receptor sites to activate the IRS proteins that enter the PI3K and PKB/AKT pathways. These pathways cross the GSK-3 and thereby produce the Tau hyper-phosphorylation characteristic for AD. The alternative pathway leads to Shc, Grb2/SOS, Ras, Raf, MAPK activation and gene expression. The absence of IGF1 leads to decreased glucose uptake, decreased glycogen and protein synthesis, an increased level of AGEs, increased Tau phosphorylation and thus increased apoptosis.