Aβ amyloidosis induces the initial stage of tau accumulation in APPSw mice

To clarify how A beta deposits induce secondary tauopathy, the presence of phosphorylated tau, glycogen synthase kinase 3 alpha (GSK3 alpha), GSK3 beta, cyclin-dependent kinase 5 (CDK5), mitogen-activated protein kinase (MAPK) and fyn were examined in the Tg2576 brain showing substantial brain A beta amyloidosis and behavioral abnormalities. Phosphorylated tau at Ser199, Thr231/Ser235, Ser396 and Ser413 accumulated in the dystrophic neurites of senile plaques. The major kinase for tau phosphorylation was GSK3 beta. Smaller contributions of GSK3 alpha, CDK5 and MAPK were suggested. Thus, brain A beta amyloidosis has a potential role in the induction of tauopathy leading to the mental disturbances of Alzheimer's disease, (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.