ALZHEIMERS-DISEASE ABNORMALLY PHOSPHORYLATED-TAU IS DEPHOSPHORYLATED BY PROTEIN PHOSPHATASE-2B (CALCINEURIN)

Abnormally hyperphosphorylated tau is the major protein subunit of pai red helical filaments in Alzheimer brains. We have examined its site-s pecific dephosphorylation by different protein phosphatases. Dephospho rylation of tau was monitored by its interaction with several phosphor ylation-dependent antibodies. Alzheimer tau was dephosphorylated by br ain protein phosphatase-2B at the abnormally phosphorylated sites Ser( 46), Ser(199), Ser(202), Ser(235), Ser(396), and Ser(404)m and its rel ative mobility on sodium dodecyl sulfate-polyacrylamide gel electropho resis shifted to that of normal tau. Protein phosphatases-1 and -2A co uld dephosphorylate only some of the above six phosphorylation sites. These results indicate that protein phosphatase-2B might be involved i n hyperphosphorylation of tau in Alzheimer's disease.