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Distinct metabolomic signature in cerebrospinal fluid in early parkinson's disease.
Mov Disord. 2017 Oct; 32(10):1401-1408.MD

Abstract

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 (Tübingen 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 (n = 18) as well as in a third and completely independent validation set (n = 36). 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 early-stage 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. © 2017 International Parkinson and Movement Disorder Society.

Authors+Show Affiliations

Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Luxembourg, Luxembourg. Integrated Biobank of Luxembourg, Luxembourg, Luxembourg.Functional Proteomics, Medizinisches Proteom-Center, Ruhr-University Bochum, Bochum, Germany.Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Luxembourg, Luxembourg.Functional Proteomics, Medizinisches Proteom-Center, Ruhr-University Bochum, Bochum, Germany.Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. German Center for Neurodegenerative Diseases, Tübingen, Germany.Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. German Center for Neurodegenerative Diseases, Tübingen, Germany.Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. German Center for Neurodegenerative Diseases, Tübingen, Germany. Department of Neurology, Christian-Albrechts-University, Kiel, Germany.Functional Proteomics, Medizinisches Proteom-Center, Ruhr-University Bochum, Bochum, Germany.Integrated Biobank of Luxembourg, Luxembourg, Luxembourg.Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Luxembourg, Luxembourg. Braunschweig Integrated Centre of Systems Biology, University of Braunschweig, Braunschweig, Germany. Department of Computational Biology of Infection Research, Helmholtz Centre for Infection Research, Braunschweig, Germany.Paracelsus-Elena Klinik, Kassel, Germany. University Medical Center Goettingen, Institute of Neuropathology and Department of Neurosurgery, Goettingen, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28843022

Citation

Trezzi, Jean-Pierre, et al. "Distinct Metabolomic Signature in Cerebrospinal Fluid in Early Parkinson's Disease." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 32, no. 10, 2017, pp. 1401-1408.
Trezzi JP, Galozzi S, Jaeger C, et al. Distinct metabolomic signature in cerebrospinal fluid in early parkinson's disease. Mov Disord. 2017;32(10):1401-1408.
Trezzi, J. P., Galozzi, S., Jaeger, C., Barkovits, K., Brockmann, K., Maetzler, W., Berg, D., Marcus, K., Betsou, F., Hiller, K., & Mollenhauer, B. (2017). Distinct metabolomic signature in cerebrospinal fluid in early parkinson's disease. Movement Disorders : Official Journal of the Movement Disorder Society, 32(10), 1401-1408. https://doi.org/10.1002/mds.27132
Trezzi JP, et al. Distinct Metabolomic Signature in Cerebrospinal Fluid in Early Parkinson's Disease. Mov Disord. 2017;32(10):1401-1408. PubMed PMID: 28843022.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinct metabolomic signature in cerebrospinal fluid in early parkinson's disease. AU - Trezzi,Jean-Pierre, AU - Galozzi,Sara, AU - Jaeger,Christian, AU - Barkovits,Katalin, AU - Brockmann,Kathrin, AU - Maetzler,Walter, AU - Berg,Daniela, AU - Marcus,Katrin, AU - Betsou,Fay, AU - Hiller,Karsten, AU - Mollenhauer,Brit, Y1 - 2017/08/26/ PY - 2017/03/31/received PY - 2017/07/14/revised PY - 2017/07/17/accepted PY - 2017/8/27/pubmed PY - 2018/6/13/medline PY - 2017/8/27/entrez KW - CSF KW - Parkinson's disease KW - biomarker KW - logistic regression KW - metabolomics SP - 1401 EP - 1408 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 32 IS - 10 N2 - 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 (Tübingen 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 (n = 18) as well as in a third and completely independent validation set (n = 36). 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 early-stage 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. © 2017 International Parkinson and Movement Disorder Society. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/28843022/Distinct_metabolomic_signature_in_cerebrospinal_fluid_in_early_parkinson's_disease_ L2 - https://doi.org/10.1002/mds.27132 DB - PRIME DP - Unbound Medicine ER -