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NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice

The development of effective therapies as well as early, molecular diagnosis of Alzheimer’s disease is impeded by the lack of understanding of the underlying pathological mechanisms. Metabolomics studies of body fluids as well as brain tissues have shown major changes in metabolic profiles of Alzhei...

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Autores principales: Stojanovic, Filip, Taktek, Mariam, Khieu, Nam Huan, Huang, Junzhou, Jiang, Susan, Rennie, Kerry, Chakravarthy, Balu, Costain, Will J., Cuperlovic-Culf, Miroslava
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109765/
https://www.ncbi.nlm.nih.gov/pubmed/33970919
http://dx.doi.org/10.1371/journal.pone.0250568
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author Stojanovic, Filip
Taktek, Mariam
Khieu, Nam Huan
Huang, Junzhou
Jiang, Susan
Rennie, Kerry
Chakravarthy, Balu
Costain, Will J.
Cuperlovic-Culf, Miroslava
author_facet Stojanovic, Filip
Taktek, Mariam
Khieu, Nam Huan
Huang, Junzhou
Jiang, Susan
Rennie, Kerry
Chakravarthy, Balu
Costain, Will J.
Cuperlovic-Culf, Miroslava
author_sort Stojanovic, Filip
collection PubMed
description The development of effective therapies as well as early, molecular diagnosis of Alzheimer’s disease is impeded by the lack of understanding of the underlying pathological mechanisms. Metabolomics studies of body fluids as well as brain tissues have shown major changes in metabolic profiles of Alzheimer’s patients. However, with analysis performed at the late stages of the disease it is not possible to distinguish causes and consequence. The mouse model APP/PS1 expresses a mutant amyloid precursor protein resulting in early Amyloid β (Aβ) accumulation as well as many resulting physiological changes including changes in metabolic profile and metabolism. Analysis of metabolic profile of cerebrospinal fluid (CSF) and blood of APP/PS1 mouse model can provide information about metabolic changes in these body fluids caused by Aβ accumulation. Using our novel method for analysis of correlation and mathematical ranking of significant correlations between metabolites in CSF and blood, we have explored changes in metabolite correlation and connectedness in APP/PS1 and wild type mice. Metabolites concentration and correlation changes in CSF, blood and across the blood brain barrier determined in this work are affected by the production of amyloid plaque. Metabolite changes observed in the APP/PS1 mouse model are the response to the mutation causing plaque formation, not the cause for the plaque suggesting that they are less relevant in the context of early treatment and prevention then the metabolic changes observed only in humans.
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spelling pubmed-81097652021-05-21 NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice Stojanovic, Filip Taktek, Mariam Khieu, Nam Huan Huang, Junzhou Jiang, Susan Rennie, Kerry Chakravarthy, Balu Costain, Will J. Cuperlovic-Culf, Miroslava PLoS One Research Article The development of effective therapies as well as early, molecular diagnosis of Alzheimer’s disease is impeded by the lack of understanding of the underlying pathological mechanisms. Metabolomics studies of body fluids as well as brain tissues have shown major changes in metabolic profiles of Alzheimer’s patients. However, with analysis performed at the late stages of the disease it is not possible to distinguish causes and consequence. The mouse model APP/PS1 expresses a mutant amyloid precursor protein resulting in early Amyloid β (Aβ) accumulation as well as many resulting physiological changes including changes in metabolic profile and metabolism. Analysis of metabolic profile of cerebrospinal fluid (CSF) and blood of APP/PS1 mouse model can provide information about metabolic changes in these body fluids caused by Aβ accumulation. Using our novel method for analysis of correlation and mathematical ranking of significant correlations between metabolites in CSF and blood, we have explored changes in metabolite correlation and connectedness in APP/PS1 and wild type mice. Metabolites concentration and correlation changes in CSF, blood and across the blood brain barrier determined in this work are affected by the production of amyloid plaque. Metabolite changes observed in the APP/PS1 mouse model are the response to the mutation causing plaque formation, not the cause for the plaque suggesting that they are less relevant in the context of early treatment and prevention then the metabolic changes observed only in humans. Public Library of Science 2021-05-10 /pmc/articles/PMC8109765/ /pubmed/33970919 http://dx.doi.org/10.1371/journal.pone.0250568 Text en © 2021 Stojanovic et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Stojanovic, Filip
Taktek, Mariam
Khieu, Nam Huan
Huang, Junzhou
Jiang, Susan
Rennie, Kerry
Chakravarthy, Balu
Costain, Will J.
Cuperlovic-Culf, Miroslava
NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice
title NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice
title_full NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice
title_fullStr NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice
title_full_unstemmed NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice
title_short NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice
title_sort nmr analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in alzheimer model male and female mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109765/
https://www.ncbi.nlm.nih.gov/pubmed/33970919
http://dx.doi.org/10.1371/journal.pone.0250568
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