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

Aims Active amyloid‐β ( A β) immunotherapy in Alzheimer's disease ( AD ) induces removal of Aβ and phosphorylated tau (ptau). Glycogen synthase kinase ( GSK )‐3β is a kinase, responsible for phosphorylation of tau, activation of which can be induced by phosphorylated double‐stranded RNA ‐dependent protein kinase (p PKR ). Using a post‐mortem cohort of immunized AD cases, we investigated the effect of A β immunization on GSK ‐3β expression and p PKR . Methods We immunostained 11 immunized AD cases and 28 unimmunized AD cases for active, inactive and total GSK ‐3β, and for p PKR . Quantification of protein load was performed in the hippocampal region including CA 1, subiculum and entorhinal cortex. Results All three areas showed a significant decrease in the three forms of GSK ‐3β ( P  < 0.05) and a nonsignificant trend towards lower p PKR load in the immunized AD cases compared with the unimmunized AD cases. Conclusion The lower GSK ‐3β expression generated by A β immunotherapy shows evidence of a modification of the signalling pathway induced by GSK ‐3β leading to the overall reduction of tau, supporting the contention that in humans, GSK ‐3β unifies A β and tau‐related neuropathology.