title: Effect of amyloid-β (Aβ) immunization on hyperphosphorylated tau: a potential role for glycogen synthase kinase (GSK)-3β.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK.|Memory Assessment and Research Centre, Moorgreen Hospital, Southern Health Foundation Trust, Southampton, UK.
authors.forename: Jay
authors.initials: J
authors.lastname: Amin
authors.affiliation: INSERM, U942, Paris, France.|Univ Paris Diderot, Sorbonne Paris Cité, UMRS 942, Paris, France.|Centre Mémoire de Ressources et de Recherche Paris Nord Ile de France, AP-HP, Hopital Lariboisière, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Paquet
authors.affiliation: Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK.|Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Baker
authors.affiliation: Centre for Biological Sciences, Faculty of Natural and Environmental Science, University of Southampton, UK.
authors.forename: Ayodeji A
authors.initials: AA
authors.lastname: Asuni
authors.affiliation: Department of Neuropathology, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Seth
authors.initials: S
authors.lastname: Love
authors.affiliation: Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK.|Memory Assessment and Research Centre, Moorgreen Hospital, Southern Health Foundation Trust, Southampton, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Holmes
authors.affiliation: INSERM, U942, Paris, France.|Univ Paris Diderot, Sorbonne Paris Cité, UMRS 942, Paris, France.|Centre Mémoire de Ressources et de Recherche Paris Nord Ile de France, AP-HP, Hopital Lariboisière, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Hugon
authors.affiliation: Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK.|Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: James A R
authors.initials: JA
authors.lastname: Nicoll
authors.affiliation: Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK.
authors.forename: Delphine
authors.initials: D
authors.lastname: Boche
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D023582:Alzheimer Vaccines / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000276:immunology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; C054369:MAPT protein, human; D016875:tau Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: Alzheimer's disease; GSK-3β; PKR; Tau; immunotherapy