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

This study set out to search for a link between overproduction of Aβ 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 Aβ25–35. Our results suggest that the Aβ 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.