Effect of Aβ immunisation on hyperphosphorylated tau: a potential role for GSK-3β

Jay Amin, Claire Paquet, Alex Baker, Ayodeji A Asuni, Seth Love, Clive Holmes, Jacques Hugon, James Ar Nicoll, Delphine Boche

Research output: Contribution to journalArticle (Academic Journal)peer-review

19 Citations (Scopus)


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 Aβ 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.

Original languageEnglish
JournalNeuropathology and Applied Neurobiology
Publication statusPublished - 9 Dec 2014

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