Hyperphosphorylation of tau and protein phosphatases in Alzheimer disease.

Aggregation of abnormal hyperphosphorylated tau to neurofibrillary tangles in affected neurons is one of the hallmarks for Alzheimer disease (AD). Studies during the last decade have strongly suggested that hyperphosphorylation of tau is site-specifically responsible for the loss of biological activity, the gain of toxic activity, and the aggregation into paired helical filaments. Hence, the abnormal hyperphosphorylation of tau appears to be critical to the pathogenesis of AD. The state of tau phosphorylation is controlled by a balance between tau phosphatase(s) activity and tau kinase(s) activity. Many studies have shown that hyperphosphorylation of tau in AD brain might be due to decreased tau phosphatase(s) activity. This article reviews the recent research advances in regulation of tau phosphorylation by phosphoseryl/phosphothreonyl protein phosphatases, and also summarizes the role of each tau phosphatase on abnormal hyperphosphorylation of tau in AD brain.