Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783690227837042688 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8109765 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT stojanovicfilip nmranalysisofthecorrelationofmetabolicchangesinbloodandcerebrospinalfluidinalzheimermodelmaleandfemalemice AT taktekmariam nmranalysisofthecorrelationofmetabolicchangesinbloodandcerebrospinalfluidinalzheimermodelmaleandfemalemice AT khieunamhuan nmranalysisofthecorrelationofmetabolicchangesinbloodandcerebrospinalfluidinalzheimermodelmaleandfemalemice AT huangjunzhou nmranalysisofthecorrelationofmetabolicchangesinbloodandcerebrospinalfluidinalzheimermodelmaleandfemalemice AT jiangsusan nmranalysisofthecorrelationofmetabolicchangesinbloodandcerebrospinalfluidinalzheimermodelmaleandfemalemice AT renniekerry nmranalysisofthecorrelationofmetabolicchangesinbloodandcerebrospinalfluidinalzheimermodelmaleandfemalemice AT chakravarthybalu nmranalysisofthecorrelationofmetabolicchangesinbloodandcerebrospinalfluidinalzheimermodelmaleandfemalemice AT costainwillj nmranalysisofthecorrelationofmetabolicchangesinbloodandcerebrospinalfluidinalzheimermodelmaleandfemalemice AT cuperlovicculfmiroslava nmranalysisofthecorrelationofmetabolicchangesinbloodandcerebrospinalfluidinalzheimermodelmaleandfemalemice |