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 A...

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Autores principales:	Filip Stojanovic, Mariam Taktek, Nam Huan Khieu, Junzhou Huang, Susan Jiang, Kerry Rennie, Balu Chakravarthy, Will J Costain, Miroslava Cuperlovic-Culf
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7ca410966c494c238d0e4caf8e431b64
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spelling	oai:doaj.org-article:7ca410966c494c238d0e4caf8e431b642021-12-02T20:05:41ZNMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice.1932-620310.1371/journal.pone.0250568https://doaj.org/article/7ca410966c494c238d0e4caf8e431b642021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0250568https://doaj.org/toc/1932-6203The 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.Filip StojanovicMariam TaktekNam Huan KhieuJunzhou HuangSusan JiangKerry RennieBalu ChakravarthyWill J CostainMiroslava Cuperlovic-CulfPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0250568 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Filip Stojanovic Mariam Taktek Nam Huan Khieu Junzhou Huang Susan Jiang Kerry Rennie Balu Chakravarthy Will J Costain Miroslava Cuperlovic-Culf NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice.
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	article
author	Filip Stojanovic Mariam Taktek Nam Huan Khieu Junzhou Huang Susan Jiang Kerry Rennie Balu Chakravarthy Will J Costain Miroslava Cuperlovic-Culf
author_facet	Filip Stojanovic Mariam Taktek Nam Huan Khieu Junzhou Huang Susan Jiang Kerry Rennie Balu Chakravarthy Will J Costain Miroslava Cuperlovic-Culf
author_sort	Filip Stojanovic
title	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_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_sort	nmr analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in alzheimer model male and female mice.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/7ca410966c494c238d0e4caf8e431b64
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NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice.

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