In addition to synaptic plasticity, neuroinflammation can negatively influence the insulin signaling cascade, and impaired activation of the insulin signaling cascade can further cause hyperphosphorylation of tau protein, one of the hallmarks of AD [41], through increased kinase activity of GSK-3β toward tau protein caused by decreased phosphorylation at inhibitory epitope Ser9. Here, MAPT is linked to Alzheimer disease.