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

First Author  Stojanovic F Year  2021
Journal  PLoS One Volume  16
Issue  5 Pages  e0250568
PubMed ID  33970919 Mgi Jnum  J:307130
Mgi Id  MGI:6712607 Doi  10.1371/journal.pone.0250568
Citation  Stojanovic F, et al. (2021) NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice. PLoS One 16(5):e0250568
abstractText  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 beta (Abeta) 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 Abeta 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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