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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
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
0305-1846
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
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), 445-457. (doi:10.1111/nan.12205). (PMID:25486988)

Record type: Article

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: https://eprints.soton.ac.uk/id/eprint/373423
ISSN: 0305-1846
PURE UUID: b17f6b0b-f0ef-4861-9ad9-a69104a57cb4
ORCID for Jay Amin: ORCID iD orcid.org/0000-0003-3792-0428
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X

Catalogue record

Date deposited: 16 Jan 2015 16:51
Last modified: 15 Aug 2019 00:49

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Contributors

Author: Jay Amin ORCID iD
Author: Claire Paquet
Author: Alex Baker
Author: Ayodeji A. Asuni
Author: Seth Love
Author: Clive Holmes ORCID iD
Author: Jacques Hugon
Author: Delphine Boche ORCID iD

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