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Serum and brain natural copper stable isotopes in a mouse model of Alzheimer’s disease

Alzheimer’s disease is associated with the production of Cu rich aβ fibrils. Because monitoring the changes in Cu level of organs has been proposed to follow the evolution of the disease, we analyzed the copper isotopic composition of serum and brain of APPswe/PSEN1dE9 transgenic mice, a model of Al...

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Autores principales: Moynier, Frédéric, Creech, John, Dallas, Jessica, Le Borgne, Marie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695409/
https://www.ncbi.nlm.nih.gov/pubmed/31417103
http://dx.doi.org/10.1038/s41598-019-47790-5
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author Moynier, Frédéric
Creech, John
Dallas, Jessica
Le Borgne, Marie
author_facet Moynier, Frédéric
Creech, John
Dallas, Jessica
Le Borgne, Marie
author_sort Moynier, Frédéric
collection PubMed
description Alzheimer’s disease is associated with the production of Cu rich aβ fibrils. Because monitoring the changes in Cu level of organs has been proposed to follow the evolution of the disease, we analyzed the copper isotopic composition of serum and brain of APPswe/PSEN1dE9 transgenic mice, a model of Alzheimer’s disease, and wild-type (WT) controls. Serum composition of 3, 6, 9 and 12-month-old mice, as well as the composition of 9 brains of 12-month-old mice are reported. In WT mice, brains were ~1‰ isotopically heavier than serum, and the Cu isotopic composition of the serum was isotopically different between males and females. We propose that this effect of sex on the Cu isotopic budget of the serum may be related to a difference of Cu speciation and relative abundance of Cu carriers. Brains of APPswe/PSEN1dE9 mice were slightly lighter than brains of WT mice, while not statistically significant. This trend may reflect an increase of Cu(I) associated with the formation of Aβ fibrils. The Cu isotopic composition of the brains and serum were correlated, implying copper transport between these two reservoirs, in particular a transfer of Cu(I) from the brain to the serum. Altogether, these data suggest that Cu stable isotopic composition of body fluid may have the potential to be used as detection tools for the formation of Aβ fibrils in the brain, but further work has to be done.
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spelling pubmed-66954092019-08-19 Serum and brain natural copper stable isotopes in a mouse model of Alzheimer’s disease Moynier, Frédéric Creech, John Dallas, Jessica Le Borgne, Marie Sci Rep Article Alzheimer’s disease is associated with the production of Cu rich aβ fibrils. Because monitoring the changes in Cu level of organs has been proposed to follow the evolution of the disease, we analyzed the copper isotopic composition of serum and brain of APPswe/PSEN1dE9 transgenic mice, a model of Alzheimer’s disease, and wild-type (WT) controls. Serum composition of 3, 6, 9 and 12-month-old mice, as well as the composition of 9 brains of 12-month-old mice are reported. In WT mice, brains were ~1‰ isotopically heavier than serum, and the Cu isotopic composition of the serum was isotopically different between males and females. We propose that this effect of sex on the Cu isotopic budget of the serum may be related to a difference of Cu speciation and relative abundance of Cu carriers. Brains of APPswe/PSEN1dE9 mice were slightly lighter than brains of WT mice, while not statistically significant. This trend may reflect an increase of Cu(I) associated with the formation of Aβ fibrils. The Cu isotopic composition of the brains and serum were correlated, implying copper transport between these two reservoirs, in particular a transfer of Cu(I) from the brain to the serum. Altogether, these data suggest that Cu stable isotopic composition of body fluid may have the potential to be used as detection tools for the formation of Aβ fibrils in the brain, but further work has to be done. Nature Publishing Group UK 2019-08-15 /pmc/articles/PMC6695409/ /pubmed/31417103 http://dx.doi.org/10.1038/s41598-019-47790-5 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Moynier, Frédéric
Creech, John
Dallas, Jessica
Le Borgne, Marie
Serum and brain natural copper stable isotopes in a mouse model of Alzheimer’s disease
title Serum and brain natural copper stable isotopes in a mouse model of Alzheimer’s disease
title_full Serum and brain natural copper stable isotopes in a mouse model of Alzheimer’s disease
title_fullStr Serum and brain natural copper stable isotopes in a mouse model of Alzheimer’s disease
title_full_unstemmed Serum and brain natural copper stable isotopes in a mouse model of Alzheimer’s disease
title_short Serum and brain natural copper stable isotopes in a mouse model of Alzheimer’s disease
title_sort serum and brain natural copper stable isotopes in a mouse model of alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695409/
https://www.ncbi.nlm.nih.gov/pubmed/31417103
http://dx.doi.org/10.1038/s41598-019-47790-5
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