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

Abstract

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.

More information

Identifiers

ORCID for Jay Amin: orcid.org/0000-0003-3792-0428

ORCID for Clive Holmes: orcid.org/0000-0003-1999-6912

ORCID for James A.R. Nicoll: orcid.org/0000-0002-9444-7246

ORCID for Delphine Boche: orcid.org/0000-0002-5884-130X

Catalogue record

Export record

Altmetrics