Effect of amyloid-β (Aβ) immunization on hyperphosphorylated tau: a potential role for glycogen synthase kinase (GSK)-3β
Effect of amyloid-β (Aβ) immunization on hyperphosphorylated tau: a potential role for glycogen synthase kinase (GSK)-3β
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.
lzheimer's disease, immunotherapy, tau, GSK-3?, PKR
445-457
Amin, Jay
692a8880-70ff-4b64-a7e9-7d0d53449a30
Paquet, Claire
4a54324b-6350-42e0-8343-3baa4a4ad53e
Baker, Alex
d68f3c27-eea8-4830-9a86-cfec7c8e2b65
Asuni, Ayodeji A.
b1412b1b-9794-4705-aada-aed5d3da038f
Love, Seth
c8c00a86-ecf8-4f61-8377-254305bdbc02
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Hugon, Jacques
de69c379-343f-42c5-ac70-0fb19eefd0bb
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
June 2015
Amin, Jay
692a8880-70ff-4b64-a7e9-7d0d53449a30
Paquet, Claire
4a54324b-6350-42e0-8343-3baa4a4ad53e
Baker, Alex
d68f3c27-eea8-4830-9a86-cfec7c8e2b65
Asuni, Ayodeji A.
b1412b1b-9794-4705-aada-aed5d3da038f
Love, Seth
c8c00a86-ecf8-4f61-8377-254305bdbc02
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Hugon, Jacques
de69c379-343f-42c5-ac70-0fb19eefd0bb
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Amin, Jay, Paquet, Claire, Baker, Alex, Asuni, Ayodeji A., Love, Seth, Holmes, Clive, Hugon, Jacques, Nicoll, James A.R. and Boche, Delphine
(2015)
Effect of amyloid-β (Aβ) immunization on hyperphosphorylated tau: a potential role for glycogen synthase kinase (GSK)-3β.
Neuropathology and Applied Neurobiology, 41 (4), .
(doi:10.1111/nan.12205).
(PMID:25486988)
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.
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Accepted/In Press date: 3 December 2014
e-pub ahead of print date: 9 December 2014
Published date: June 2015
Keywords:
lzheimer's disease, immunotherapy, tau, GSK-3?, PKR
Organisations:
Faculty of Medicine
Identifiers
Local EPrints ID: 373423
URI: http://eprints.soton.ac.uk/id/eprint/373423
ISSN: 0305-1846
PURE UUID: b17f6b0b-f0ef-4861-9ad9-a69104a57cb4
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Date deposited: 16 Jan 2015 16:51
Last modified: 05 Oct 2024 01:51
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Contributors
Author:
Claire Paquet
Author:
Alex Baker
Author:
Ayodeji A. Asuni
Author:
Seth Love
Author:
Jacques Hugon
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