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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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IOS Press
2020
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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. |
format | Online Article Text |
id | pubmed-7458552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
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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