Alzheimer's Disease Abnormally Phosphorylated τ Is Dephosphorylated by Protein Phosphatase‐2B (Calcineurin)

Abnormally hyperphosphorylated tau is the major protein subunit of paired helical filaments in Alzheimer brains. We have examined its site-specific dephosphorylation by different protein phosphatases. Dephosphorylation of tau was monitored by its interaction with several phosphorylation-dependent antibodies. Alzheimer tau was dephosphorylated by brain protein phosphatase-2B at the abnormally phosphorylated sites Ser46, Ser199, Ser202, Ser235, Ser396, and Ser404, and its relative mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis shifted to that of normal tau. Protein phosphatases-1 and -2A could dephosphorylate only some of the above six phosphorylation sites. These results indicate that protein phosphatase-2B might be involved in hyperphosphorylation of tau in Alzheimer's disease.