MAPT and Alzheimer disease: Phosphorylation of tau at specific residues, most notably Ser202, Ser396, Ser404, Thr181, and Thr231, is thought to induce conformational changes that create a positive feedback loop where tau is hyperphosphorylated via sequential phosphorylation at multiple sites, although the exact relationship between these residues and AD requires further defining [135,136,137,138].