Impaired brain insulin signaling, either as a result of insulin resistance due to the chronic exposure of neurons to high levels of insulin (Kim et al., 2011), or as a result of eventual decrease in brain insulin levels, triggers a reduction in AkT phosphorylation that leads to an increase in GSK3β activity and ultimately Tau phosphorylation (Zhang et al., 2018). Here, MAPT is linked to Insulin resistance.