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Metabolomic Profiling of Bile Acids in an Experimental Model of Prodromal Parkinson’s Disease

For people with Parkinson’s disease (PD), considered the most common neurodegenerative disease behind Alzheimer’s disease, accurate diagnosis is dependent on many factors; however, misdiagnosis is extremely common in the prodromal phases of the disease, when treatment is thought to be most effective...

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Autores principales: Graham, Stewart F., Rey, Nolwen L., Ugur, Zafer, Yilmaz, Ali, Sherman, Eric, Maddens, Michael, Bahado-Singh, Ray O., Becker, Katelyn, Schulz, Emily, Meyerdirk, Lindsay K., Steiner, Jennifer A., Ma, Jiyan, Brundin, Patrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316593/
https://www.ncbi.nlm.nih.gov/pubmed/30384419
http://dx.doi.org/10.3390/metabo8040071
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author Graham, Stewart F.
Rey, Nolwen L.
Ugur, Zafer
Yilmaz, Ali
Sherman, Eric
Maddens, Michael
Bahado-Singh, Ray O.
Becker, Katelyn
Schulz, Emily
Meyerdirk, Lindsay K.
Steiner, Jennifer A.
Ma, Jiyan
Brundin, Patrik
author_facet Graham, Stewart F.
Rey, Nolwen L.
Ugur, Zafer
Yilmaz, Ali
Sherman, Eric
Maddens, Michael
Bahado-Singh, Ray O.
Becker, Katelyn
Schulz, Emily
Meyerdirk, Lindsay K.
Steiner, Jennifer A.
Ma, Jiyan
Brundin, Patrik
author_sort Graham, Stewart F.
collection PubMed
description For people with Parkinson’s disease (PD), considered the most common neurodegenerative disease behind Alzheimer’s disease, accurate diagnosis is dependent on many factors; however, misdiagnosis is extremely common in the prodromal phases of the disease, when treatment is thought to be most effective. Currently, there are no robust biomarkers that aid in the early diagnosis of PD. Following previously reported work by our group, we accurately measured the concentrations of 18 bile acids in the serum of a prodromal mouse model of PD. We identified three bile acids at significantly different concentrations (p < 0.05) when mice representing a prodromal PD model were compared with controls. These include ω-murichoclic acid (MCAo), tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA). All were down-regulated in prodromal PD mice with TUDCA and UDCA at significantly lower levels (17-fold and 14-fold decrease, respectively). Using the concentration of three bile acids combined with logistic regression, we can discriminate between prodromal PD mice from control mice with high accuracy (AUC (95% CI) = 0.906 (0.777–1.000)) following cross validation. Our study highlights the need to investigate bile acids as potential biomarkers that predict PD and possibly reflect the progression of manifest PD.
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spelling pubmed-63165932019-01-10 Metabolomic Profiling of Bile Acids in an Experimental Model of Prodromal Parkinson’s Disease Graham, Stewart F. Rey, Nolwen L. Ugur, Zafer Yilmaz, Ali Sherman, Eric Maddens, Michael Bahado-Singh, Ray O. Becker, Katelyn Schulz, Emily Meyerdirk, Lindsay K. Steiner, Jennifer A. Ma, Jiyan Brundin, Patrik Metabolites Article For people with Parkinson’s disease (PD), considered the most common neurodegenerative disease behind Alzheimer’s disease, accurate diagnosis is dependent on many factors; however, misdiagnosis is extremely common in the prodromal phases of the disease, when treatment is thought to be most effective. Currently, there are no robust biomarkers that aid in the early diagnosis of PD. Following previously reported work by our group, we accurately measured the concentrations of 18 bile acids in the serum of a prodromal mouse model of PD. We identified three bile acids at significantly different concentrations (p < 0.05) when mice representing a prodromal PD model were compared with controls. These include ω-murichoclic acid (MCAo), tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA). All were down-regulated in prodromal PD mice with TUDCA and UDCA at significantly lower levels (17-fold and 14-fold decrease, respectively). Using the concentration of three bile acids combined with logistic regression, we can discriminate between prodromal PD mice from control mice with high accuracy (AUC (95% CI) = 0.906 (0.777–1.000)) following cross validation. Our study highlights the need to investigate bile acids as potential biomarkers that predict PD and possibly reflect the progression of manifest PD. MDPI 2018-10-31 /pmc/articles/PMC6316593/ /pubmed/30384419 http://dx.doi.org/10.3390/metabo8040071 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Graham, Stewart F.
Rey, Nolwen L.
Ugur, Zafer
Yilmaz, Ali
Sherman, Eric
Maddens, Michael
Bahado-Singh, Ray O.
Becker, Katelyn
Schulz, Emily
Meyerdirk, Lindsay K.
Steiner, Jennifer A.
Ma, Jiyan
Brundin, Patrik
Metabolomic Profiling of Bile Acids in an Experimental Model of Prodromal Parkinson’s Disease
title Metabolomic Profiling of Bile Acids in an Experimental Model of Prodromal Parkinson’s Disease
title_full Metabolomic Profiling of Bile Acids in an Experimental Model of Prodromal Parkinson’s Disease
title_fullStr Metabolomic Profiling of Bile Acids in an Experimental Model of Prodromal Parkinson’s Disease
title_full_unstemmed Metabolomic Profiling of Bile Acids in an Experimental Model of Prodromal Parkinson’s Disease
title_short Metabolomic Profiling of Bile Acids in an Experimental Model of Prodromal Parkinson’s Disease
title_sort metabolomic profiling of bile acids in an experimental model of prodromal parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316593/
https://www.ncbi.nlm.nih.gov/pubmed/30384419
http://dx.doi.org/10.3390/metabo8040071
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