Hyper-phosphorylation of tau at proline directed serine/threonine phosphorylation sites leads to neurofibrillary tangle formation, which is another hallmark of AD along with Aβ plaque accumulation (Yuzwa et al., 2008; Selnick et al., 2019; Shcherbinin et al., 2020; Permanne et al., 2022; Yin et al., 2022). This evidence concerns the gene MAPT and Alzheimer disease.