Effect of amyloid-β (Aβ) immunization on hyperphosphorylated tau: a potential role for glycogen synthase kinase (GSK)-3β

AimsActive amyloid- (A) immunotherapy in Alzheimer's disease (AD) induces removal of A and phosphorylated tau (ptau). Glycogen synthase kinase (GSK)-3 is a kinase, responsible for phosphorylation of tau, activation of which can be induced by phosphorylated double-stranded RNA-dependent protein kinase (pPKR). Using a post-mortem cohort of immunized AD cases, we investigated the effect of A immunization on GSK-3 expression and pPKR. MethodsWe immunostained 11 immunized AD cases and 28 unimmunized AD cases for active, inactive and total GSK-3, and for pPKR. Quantification of protein load was performed in the hippocampal region including CA1, subiculum and entorhinal cortex. ResultsAll three areas showed a significant decrease in the three forms of GSK-3 (P<0.05) and a nonsignificant trend towards lower pPKR load in the immunized AD cases compared with the unimmunized AD cases. ConclusionThe lower GSK-3 expression generated by A immunotherapy shows evidence of a modification of the signalling pathway induced by GSK-3 leading to the overall reduction of tau, supporting the contention that in humans, GSK-3 unifies A and tau-related neuropathology.