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Vaccination Prevented Short-Term Memory Loss, but Deteriorated Long-Term Spatial Memory in Alzheimer’s Disease Mice, Independent of Amyloid-β Pathology

BACKGROUND: Soluble oligomeric amyloid-β (Aβ), rather than Aβ plaques, seems to be the culprit in Alzheimer’s disease (AD). Accordingly, a new concept vaccine of small cyclic peptide conjugates, selectively targeting oligomeric Aβ, has been developed. OBJECTIVE: Study the therapeutic potential of th...

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Autores principales: Oberman, Klaske, Gouweleeuw, Leonie, Hoogerhout, Peter, Eisel, Ulrich L.M., van Riet, Elly, Schoemaker, Regien G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458552/
https://www.ncbi.nlm.nih.gov/pubmed/32904788
http://dx.doi.org/10.3233/ADR-200213
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author Oberman, Klaske
Gouweleeuw, Leonie
Hoogerhout, Peter
Eisel, Ulrich L.M.
van Riet, Elly
Schoemaker, Regien G.
author_facet Oberman, Klaske
Gouweleeuw, Leonie
Hoogerhout, Peter
Eisel, Ulrich L.M.
van Riet, Elly
Schoemaker, Regien G.
author_sort Oberman, Klaske
collection PubMed
description BACKGROUND: Soluble oligomeric amyloid-β (Aβ), rather than Aβ plaques, seems to be the culprit in Alzheimer’s disease (AD). Accordingly, a new concept vaccine of small cyclic peptide conjugates, selectively targeting oligomeric Aβ, has been developed. OBJECTIVE: Study the therapeutic potential of this new vaccine in a mouse model for AD. METHODS: J20 mice, overexpressing human amyloid precursor protein, were validated for an AD-like phenotype. Then, J20 mice were vaccinated at 2, 3, and 4 months of age and AD phenotype was evaluated at 6, 9, and 12 months of age; or at 9, 10, and 11 months with evaluation at 12 months. Effects on Aβ pathology were studied by plaque load (immunohistochemistry; 6E10) and antibody titers against Aβ (ELISA). AD behavioral phenotype was evaluated by performance in a battery of cognitive tests. RESULTS: J20 mice displayed age-related Aβ plaque development and an AD-like behavioral phenotype. A consistent antibody response to the cyclic peptides was, however, not extended to Aβ, leaving plaque load unaffected. Nevertheless, immunization at young ages prevented working- and short-term spatial memory loss, but deteriorated long-term spatial learning and memory, at 12 months of age. Immunization at later ages did not affect any measured parameter. CONCLUSION: J20 mice provide a relevant model for AD to study potential anti-Aβ treatment. Early vaccination prevented short-term memory loss at later ages, but deteriorated long-term spatial memory, however without affecting Aβ pathology. Later vaccination had no effects, but optimal timing may require further investigation.
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spelling pubmed-74585522020-09-03 Vaccination Prevented Short-Term Memory Loss, but Deteriorated Long-Term Spatial Memory in Alzheimer’s Disease Mice, Independent of Amyloid-β Pathology Oberman, Klaske Gouweleeuw, Leonie Hoogerhout, Peter Eisel, Ulrich L.M. van Riet, Elly Schoemaker, Regien G. J Alzheimers Dis Rep Research Article BACKGROUND: Soluble oligomeric amyloid-β (Aβ), rather than Aβ plaques, seems to be the culprit in Alzheimer’s disease (AD). Accordingly, a new concept vaccine of small cyclic peptide conjugates, selectively targeting oligomeric Aβ, has been developed. OBJECTIVE: Study the therapeutic potential of this new vaccine in a mouse model for AD. METHODS: J20 mice, overexpressing human amyloid precursor protein, were validated for an AD-like phenotype. Then, J20 mice were vaccinated at 2, 3, and 4 months of age and AD phenotype was evaluated at 6, 9, and 12 months of age; or at 9, 10, and 11 months with evaluation at 12 months. Effects on Aβ pathology were studied by plaque load (immunohistochemistry; 6E10) and antibody titers against Aβ (ELISA). AD behavioral phenotype was evaluated by performance in a battery of cognitive tests. RESULTS: J20 mice displayed age-related Aβ plaque development and an AD-like behavioral phenotype. A consistent antibody response to the cyclic peptides was, however, not extended to Aβ, leaving plaque load unaffected. Nevertheless, immunization at young ages prevented working- and short-term spatial memory loss, but deteriorated long-term spatial learning and memory, at 12 months of age. Immunization at later ages did not affect any measured parameter. CONCLUSION: J20 mice provide a relevant model for AD to study potential anti-Aβ treatment. Early vaccination prevented short-term memory loss at later ages, but deteriorated long-term spatial memory, however without affecting Aβ pathology. Later vaccination had no effects, but optimal timing may require further investigation. IOS Press 2020-07-23 /pmc/articles/PMC7458552/ /pubmed/32904788 http://dx.doi.org/10.3233/ADR-200213 Text en © 2020 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Oberman, Klaske
Gouweleeuw, Leonie
Hoogerhout, Peter
Eisel, Ulrich L.M.
van Riet, Elly
Schoemaker, Regien G.
Vaccination Prevented Short-Term Memory Loss, but Deteriorated Long-Term Spatial Memory in Alzheimer’s Disease Mice, Independent of Amyloid-β Pathology
title Vaccination Prevented Short-Term Memory Loss, but Deteriorated Long-Term Spatial Memory in Alzheimer’s Disease Mice, Independent of Amyloid-β Pathology
title_full Vaccination Prevented Short-Term Memory Loss, but Deteriorated Long-Term Spatial Memory in Alzheimer’s Disease Mice, Independent of Amyloid-β Pathology
title_fullStr Vaccination Prevented Short-Term Memory Loss, but Deteriorated Long-Term Spatial Memory in Alzheimer’s Disease Mice, Independent of Amyloid-β Pathology
title_full_unstemmed Vaccination Prevented Short-Term Memory Loss, but Deteriorated Long-Term Spatial Memory in Alzheimer’s Disease Mice, Independent of Amyloid-β Pathology
title_short Vaccination Prevented Short-Term Memory Loss, but Deteriorated Long-Term Spatial Memory in Alzheimer’s Disease Mice, Independent of Amyloid-β Pathology
title_sort vaccination prevented short-term memory loss, but deteriorated long-term spatial memory in alzheimer’s disease mice, independent of amyloid-β pathology
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458552/
https://www.ncbi.nlm.nih.gov/pubmed/32904788
http://dx.doi.org/10.3233/ADR-200213
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