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

• Main Authors: Amin, Jay (Author), Paquet, Claire (Author), Baker, Alex (Author), Asuni, Ayodeji A. (Author), Love, Seth (Author), Holmes, Clive (Author), Hugon, Jacques (Author), Nicoll, James A.R (Author), Boche, Delphine (Author)
• Format: Article
• Language: English
• Published: 2015-06.
• Subjects: Article
• Online Access: Get fulltext

 Aims Active Aβ 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 (pPKR). Using a post-mortem cohort of immunised AD cases, we investigated the effect of Abeta immunisation on GSK-3β expression and pPKR. Methods We immunostained 11 immunised AD cases and 28 unimmunised AD cases for active, inactive and total GSK-3β, and for pPKR. Quantification of protein load was performed in the hippocampal region including CA1, subiculum and entorhinal cortex. Results All 3 areas showed a significant decrease in the three forms of GSK-3β (P<0.05) and a non-significant trend towards lower pPKR load in the immunised AD cases compared to the unimmunised AD cases. Conclusion The lower GSK-3β expression generated by Aβ 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 Aβ and tau-related neuropathology.