Hyperphosphorylation of Tau in Alzheimer’s disease (AD) brain appears to be caused by a down-regulation of protein phosphatase 2A (PP2A). In this study, we selectively inhibited PP2A by injection of okadaic acid (OA) into the Meynert nucleus basalis of rats and found that 0.4 pmol of OA injection induced approximately 60% inhibition of PP2A 24 h after injection, 13% inhibition 48 h after injection and no obvious inhibition 72 h after injection. Hyperphosphorylation of Tau at Ser-198/Ser-199/Ser-202 and Ser-396/Ser-404 and spatial memory deficit of rats were induced 24 h after 0.4 pmol of OA injection. This study suggests that a down-regulation of PP2A may underlie abnormal hyperphosphorylation of cytoskeletal proteins leading to neurofibrillary degeneration in AD.
