Article (Scientific journals)
Distinct metabolomic signature in cerebrospinal fluid in early parkinson's disease: Early Parkinson'S CSF Metabolic Signature
Trezzi, Jean-Pierre; Galozzi, Sara; Jäger, Christian et al.
2017In Movement Disorders
Peer reviewed
 

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Keywords :
metabolomics; CSF; biomarker; Parkinson’s disease; logistic regression
Abstract :
[en] Objective: The purpose of this study was to profile cerebrospinal fluid (CSF) from early-stage PD patients for disease-related metabolic changes and to determine a robust biomarker signature for early-stage PD diagnosis. Methods: By applying a non-targeted and mass spectrometry-driven approach, we investigated the CSF metabolome of 44 early-stage sporadic PD patients yet without treatment (DeNoPa cohort). We compared all detected metabolite levels with those measured in CSF of 43 age- and gender-matched healthy controls. After this analysis, we validated the results in an independent PD study cohort (T€ubingen cohort). Results: We identified that dehydroascorbic acid levels were significantly lower and fructose, mannose, and threonic acid levels were significantly higher (P <.05) in PD patients when compared with healthy controls. These changes reflect pathological oxidative stress responses, as well as protein glycation/glycosylation reactions in PD. Using a machine learning approach based on logistic regression, we successfully predicted the origin (PD patients vs healthy controls) in a second (n518) as well as in a third and completely independent validation set (n536). The biomarker signature is composed of the three markers—mannose, threonic acid, and fructose—and allows for sample classification with a sensitivity of 0.790 and a specificity of 0.800. Conclusion: We identified PD-specific metabolic changes in CSF that were associated with antioxidative stress response, glycation, and inflammation. Our results disentangle the complexity of the CSF metabolome to unravel metabolome changes related to earlystage PD. The detected biomarkers help understanding PD pathogenesis and can be applied as biomarkers to increase clinical diagnosis accuracy and patient care in early-stage PD.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB)
IBBL - Integrated BioBank of Luxembourg
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Trezzi, Jean-Pierre 
Galozzi, Sara
Jäger, Christian  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Barkovits, Katalin
Brockmann, Kathrin
Maetzler, Walter
Berg, Daniela
Marcus, Katrin
Betsou, Fay
Hiller, Karsten 
Mollenhauer, Brit
External co-authors :
yes
Language :
English
Title :
Distinct metabolomic signature in cerebrospinal fluid in early parkinson's disease: Early Parkinson'S CSF Metabolic Signature
Publication date :
26 August 2017
Journal title :
Movement Disorders
ISSN :
0885-3185
Peer reviewed :
Peer reviewed
Focus Area :
Systems Biomedicine
Available on ORBilu :
since 19 September 2017

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