MAPT and Alzheimer disease: During AD onset, tau Thr 231 and Ser 262 appear to be phosphorylated early on,63, 64, 65 and phosphorylation of Thr 231 leads to the phosphorylation of Ser 199, Ser 396, Ser 400, and Ser 404,66 which manifests in the hyperphosphorylation of tau.63