Parallel increase in p70 kinase activation and tau phosphorylation (S262) with A beta overproduction

This study set out to search for a link between overproduction of A beta and p70S6 kinase (p70S6K) phosphorylation/activation. Results showed that levels of p-p70S6K at T421/S424 and T389 are significantly increased in mouse N2a neuroblastoma cells carrying human APP with Swedish mutation (APPswe), and in transgenic APPswe/PS1 (A246E) mice as compared with respective controls, corresponding to the increase of tau phosphorylation at S262. This parallel increase in p70S6K activation and tau phosphorylation could be demonstrated by treating wild-type N2a cells with A beta 25-35. Our results suggest that the A beta deposition in senile plaques in Alzheimer disease brains might be a primary event that activates p70S6K and phosphorylates tau at S262, resulting in microtubule disruption. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.