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NMR analysis of the CSF and plasma metabolome of rigorously matched amyotrophic lateral sclerosis, Parkinson's disease and control subjects
Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
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2016 (English)In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 12, no 6, 101Article in journal (Refereed) PublishedText
Abstract [en]

Introduction: Amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) are two severe neurodegenerative disorders for which the disease mechanisms are poorly understood and reliable biomarkers are absent.

Objectives: To identify metabolite biomarkers for ALS and PD, and to gain insights into which metabolic pathways are involved in disease.

Methods: Nuclear magnetic resonance (NMR) metabolomics was utilized to characterize the metabolite profiles of cerebrospinal fluid (CSF) and plasma from individuals in three age, gender, and sampling-date matched groups, comprising 22 ALS, 22 PD and 28 control subjects.

Results: Multivariate analysis of NMR data generated robust discriminatory models for separation of ALS from control subjects. ALS patients showed increased concentrations of several metabolites in both CSF and plasma, these are alanine (CSF fold change = 1.22, p = 0.005), creatine (CSF-fc = 1.17, p = 0.001), glucose (CSF-fc = 1.11, p = 0.036), isoleucine (CSF-fc = 1.24, p = 0.002), and valine (CSF-fc = 1.17, p = 0.014). Additional metabolites in CSF (creatinine, dimethylamine and lactic acid) and plasma (acetic acid, glutamic acid, histidine, leucine, pyruvate and tyrosine) were also important for this discrimination. Similarly, panels of CSF-metabolites that discriminate PD from ALS and control subjects were identified.

Conclusions: The results for the ALS patients suggest an affected creatine/creatinine pathway and an altered branched chain amino acid (BCAA) metabolism, and suggest links to glucose and energy metabolism. Putative metabolic markers specific for ALS (e.g. creatinine and lactic acid) and PD (e.g. 3-hydroxyisovaleric acid and mannose) were identified, while several (e.g. creatine and BCAAs) were shared between ALS and PD, suggesting some overlap in metabolic alterations in these disorders.

Place, publisher, year, edition, pages
2016. Vol. 12, no 6, 101
Keyword [en]
Amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), NMR metabolomics, Biomarker, rebrospinal fluid (CSF), Plasma
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-124194DOI: 10.1007/s11306-016-1041-6ISI: 000378752900006OAI: oai:DiVA.org:umu-124194DiVA: diva2:950961
Available from: 2016-08-04 Created: 2016-07-28 Last updated: 2016-08-04Bibliographically approved

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Department of ChemistryDepartment of Pharmacology and Clinical NeuroscienceDepartment of Medical Biosciences
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