Microtubule-associated protein tau is abnormally hyperphosphorylated and 
aggregated in affected neurons of Alzheimer disease brain. This 
hyperphosphorylated tau can be dephosphorylated at some of the abnormal 
phosphorylated sites by purified protein phosphatase-1, 2A, and 2B in vitro. In 
the present study, we have developed an assay to measure protein phosphatase 
activity toward tau-1 sites (Ser199/Ser202) using the hyperphosphorylated tau 
isolated from Alzheimer disease brain as substrate. Using this assay, we have 
identified that in normal brain, protein phosphatase-2A and 2B and, to a lesser 
extent, 1 are involved in the dephosphorylation of tau. The Km values of 
dephosphorylation of the hyperphosphorylated tau by protein phosphatase-2A and 
2B are similar. The tau phosphatase activity is decreased by approximately 30% 
in brain of Alzheimer disease patients compared with those of age-matched 
controls. These findings suggest that a defect of protein phosphatase could be 
the cause of the abnormal hyperphosphorylation of tau in Alzheimer disease.