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Updated: Apr 19, 2026
Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia
Published on: November 9, 2018
Effect of amyloid-β (Aβ) immunization on hyperphosphorylated tau: a potential role for glycogen synthase kinase
Jay Amin1,2, Claire Paquet3,4,5, Alex Baker1,6
1Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK.
Aims:
Active amyloid-β (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 immunized AD cases, we investigated the effect of Aβ immunization on GSK-3β expression and pPKR.
Methods:
We immunostained 11 immunized AD cases and 28 unimmunized 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 three areas showed a significant decrease in the three forms of GSK-3β (P < 0.05) and a nonsignificant trend towards lower pPKR load in the immunized AD cases compared with the unimmunized 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.
