Skip to main content

Advertisement

Log in

Metabolomic analysis of urine and serum in Parkinson’s disease

  • Original Article
  • Published:
Metabolomics Aims and scope Submit manuscript

Abstract

Objective To investigate the metabolic profile of serum and urine samples from 23 female patients with Parkinson’s disease (PD) and 23 age and sex-matched controls. Methods We used gas chromatography coupled to mass spectrometry to detect metabolites (approximately 1,600 in total), then supervised statistical analysis (using projection to latent structures discriminant analysis) to study the differences between control and PD samples. Results Supervised statistical analysis yielded models that possessed statistically significant predictive value for blind samples on the basis of the metabolic profile of urine but not of serum. However, whilst no individual biomarkers were identified, suggesting that any metabolic disturbance associated with PD is comparatively minor, a multivariate metabolic signature associated with PD was identified in urine. Interpretation There is a relatively subtle, yet distinct, metabolic signature of PD present in the urine of patients with early disease. The signature may itself act as a useful biomarker for PD, although larger studies will be required to validate our present findings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abdi, F., Quinn, J. F., Jankovic, J., McIntosh, M., Leverenz, J. B., Peskind, E., Nixon, R., Nutt, J., Chung, K., Zabetian, C., Samii, A., Lin, M., Hattan, S., Pan, C., Wang, Y., Jin, J., Zhu, D., Li, G. J., Liu, Y., Waichunas, D., Montine, T. J., & Zhang, J. (2006). Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. Journal of Alzheimer's Disease, 9(3), 293–348.

    PubMed  CAS  Google Scholar 

  • Bohnen, N. I., Kaufer, D. I., Ivanco, L. S., Lopresti, B., Koeppe, R. A., Davis, J. G., Mathis, C. A., Moore, R. Y., & DeKosky, S. T. (2003). Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: An in vivo positron emission tomographic study. Archives of Neurology, 60, 1745–1748. doi:10.1001/archneur.60.12.1745.

    Article  PubMed  Google Scholar 

  • Braak, H., Del Tredici, K., Rub, U., de Vos, R. A., Jansen Steur, E. N., & Braak, E. (2003). Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging, 24, 197–211. doi:10.1016/S0197-4580(02)00065-9.

    Article  PubMed  Google Scholar 

  • Brindle, J. T., Antti, H., Holmes, E., Tranter, G., Nicholson, J. K., Bethell, H. W., Clarke, S., Schofield, P. M., McKilligin, E., Mosedale, D. E., & Grainger, D. J. (2002). Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics. Nature Medicine, 8, 1439–1444. doi:10.1038/nm802.

    Article  PubMed  CAS  Google Scholar 

  • Brindle, J. T., Nicholson, J. K., Schofield, P. M., Grainger, D. J., & Holmes, E. (2003). Application of chemometrics to 1H NMR spectroscopic data to investigate a relationship between human serum metabolic profiles and hypertension. Analyst, 128, 32–36. doi:10.1039/b209155k.

    Article  PubMed  CAS  Google Scholar 

  • Burn, D. J., & Lees, A. J. (2002). Progressive supranuclear palsy: Where are we now? Lancet Neurology, 1, 359–369. doi:10.1016/S1474-4422(02)00161-8.

    Article  PubMed  Google Scholar 

  • Di Monte, D. A. (2003). The environment and Parkinson’s disease: Is the nigrostriatal system preferentially targeted by neurotoxins? Lancet Neurology, 2, 531–538. doi:10.1016/S1474-4422(03)00501-5.

    Article  PubMed  CAS  Google Scholar 

  • Dunn, W. B., Bailey, N. J., & Johnson, H. E. (2005). Measuring the metabolome: Current analytical technologies. Analyst, 130, 606–625. doi:10.1039/b418288j.

    Article  PubMed  CAS  Google Scholar 

  • Dunne, V. G., Bhattachayya, S., Besser, M., Rae, C., & Griffin, J. L. (2005). Metabolites from cerebrospinal fluid in aneurysmal subarachnoid haemorrhage correlate with vasospasm and clinical outcome: A pattern-recognition 1H NMR study. NMR in Biomedicine, 18, 24–33. doi:10.1002/nbm.918.

    Article  PubMed  CAS  Google Scholar 

  • Edwards, L. L., Quigley, E. M., & Pfeiffer, R. F. (1992). Gastrointestinal dysfunction in Parkinson’s disease: Frequency and pathophysiology. Neurology, 42, 726–732.

    PubMed  CAS  Google Scholar 

  • Fearnley, J. M., & Lees, A. J. (1991). Ageing and Parkinson’s disease: Substantia nigra regional selectivity. Brain, 114(Pt 5), 2283–2301. doi:10.1093/brain/114.5.2283.

    Article  PubMed  Google Scholar 

  • Foltynie, T., Brayne, C., & Barker, R. A. (2002). The heterogeneity of idiopathic Parkinson’s disease. Journal of Neurology, 249, 138–145. doi:10.1007/PL00007856.

    Article  PubMed  Google Scholar 

  • Gavaghan, C. L., Holmes, E., Lenz, E., Wilson, I. D., & Nicholson, J. K. (2000). An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences: Application to the C57BL10J and Alpk:ApfCD mouse. FEBS Letters, 484, 169–174. doi:10.1016/S0014-5793(00)02147-5.

    Article  PubMed  CAS  Google Scholar 

  • Ghauri, F. Y., Nicholson, J. K., Sweatman, B. C., Wood, J., Beddell, C. R., Lindon, J. C., & Cairns, N. J. (1993). NMR spectroscopy of human post mortem cerebrospinal fluid: Distinction of Alzheimer’s disease from control using pattern recognition and statistics. NMR in Biomedicine, 6, 163–167. doi:10.1002/nbm.1940060210.

    Article  PubMed  CAS  Google Scholar 

  • Gibb, W. R., & Lees, A. J. (1988). The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. Journal of Neurology, Neurosurgery, and Psychiatry, 51, 745–752.

    PubMed  CAS  Google Scholar 

  • Griffin, J. L. (2003). Metabonomics: NMR spectroscopy and pattern recognition analysis of body fluids and tissues for characterisation of xenobiotic toxicity and disease diagnosis. Current Opinion in Chemical Biology, 7, 648–654. doi:10.1016/j.cbpa.2003.08.008.

    Article  PubMed  CAS  Google Scholar 

  • Hughes, A. J., Daniel, S. E., Ben Shlomo, Y., & Lees, A. J. (2002). The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain, 125, 861–870. doi:10.1093/brain/awf080.

    Article  PubMed  Google Scholar 

  • Hughes, A. J., Daniel, S. E., Kilford, L., & Lees, A. J. (1992). Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: A clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery, and Psychiatry, 55, 181–184.

    PubMed  CAS  Google Scholar 

  • Kirschenlohr, H. L., Griffin, J. L., Clarke, S. C., Rhydwen, R., Grace, A. A., Schofield, P. M., Brindle, K. M., & Metcalfe, J. C. (2006). Proton NMR analysis of plasma is a weak predictor of coronary artery disease. Nature Medicine, 12(6), 705–710. doi:10.1038/nm1432.

    Article  PubMed  CAS  Google Scholar 

  • Lenz, E. M., Bright, J., Wilson, I. D., Hughes, A., Morrisson, J., Lindberg, H., & Lockton, A. (2004). Metabonomics, dietary influences and cultural differences: A 1H NMR-based study of urine samples obtained from healthy British and Swedish subjects. Journal of Pharmaceutical and Biomedical Analysis, 36, 841–849. doi:10.1016/j.jpba.2004.08.002.

    Article  PubMed  CAS  Google Scholar 

  • Lewis, S. J., Foltynie, T., Blackwell, A. D., Robbins, T. W., Owen, A. M., & Barker, R. A. (2005). Heterogeneity of Parkinson’s disease in the early clinical stages using a data driven approach. Journal of Neurology, Neurosurgery, and Psychiatry, 76, 343–348. doi:10.1136/jnnp.2003.033530.

    Article  PubMed  CAS  Google Scholar 

  • Lindon, J. C., Nicholson, J. K., Holmes, E., Antti, H., Bollard, M. E., Keun, H., Beckonert, O., Ebbels, T. M., Reily, M. D., Robertson, D., Stevens, G. J., Luke, P., Breau, A. P., Cantor, G. H., Bible, R. H., Niederhauser, U., Senn, H., Schlotterbeck, G., Sidelmann, U. G., Laursen, S. M., Tymiak, A., Car, B. D., Lehman-McKeeman, L., Colet, J. M., Loukaci, A., & Thomas, C. (2003). Contemporary issues in toxicology the role of metabonomics in toxicology and its evaluation by the COMET project. Toxicology and Applied Pharmacology, 187, 137–146. doi:10.1016/S0041-008X(02)00079-0.

    Article  PubMed  CAS  Google Scholar 

  • Mauborgne, A., Javoy-Agid, F., Legrand, J. C., Agid, Y., & Cesselin, F. (1983). Decrease of substance P-like immunoreactivity in the substantia nigra and pallidum of parkinsonian brains. Brain Research, 268, 167–170. doi:10.1016/0006-8993(83)90403-1.

    Article  PubMed  CAS  Google Scholar 

  • Mayeux, R., Chen, J., Mirabello, E., Marder, K., Bell, K., Dooneief, G., Cote, L., & Stern, Y. (1990). An estimate of the incidence of dementia in idiopathic Parkinson’s disease. Neurology, 40, 1513–1517.

    PubMed  CAS  Google Scholar 

  • Michell, A. W., Lewis, S. J., Foltynie, T., & Barker, R. A. (2004). Biomarkers and Parkinson’s disease. Brain, 127, 1693–1705. doi:10.1093/brain/awh198.

    Article  PubMed  CAS  Google Scholar 

  • Michell, A. W., Luheshi, L. M., & Barker, R. A. (2005). Skin and platelet alpha-synuclein as peripheral biomarkers of Parkinson’s disease. Neuroscience Letters, 381, 294–298. doi:10.1016/j.neulet.2005.02.030.

    Article  PubMed  CAS  Google Scholar 

  • Mikolaenko, I., Pletnikova, O., Kawas, C. H., O’Brien, R., Resnick, S. M., Crain, B., & Troncoso, J. C. (2005). Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer disease: evidence from the Baltimore Longitudinal Study of Aging (BLSA). Journal of Neuropathology and Experimental Neurology, 64, 156–162.

    PubMed  CAS  Google Scholar 

  • Nicholson, J. K., Connelly, J., Lindon, J. C., & Holmes, E. (2002). Metabonomics: A platform for studying drug toxicity and gene function. Nature Reviews Drug Discovery, 1, 153–161. doi:10.1038/nrd728.

    Article  PubMed  CAS  Google Scholar 

  • Nicholson, J. K., & Wilson, I. D. (2003). Opinion: understanding ‘global’ systems biology: metabonomics and the continuum of metabolism. Nature Reviews Drug Discovery, 2, 668–676. doi:10.1038/nrd1157.

    Article  PubMed  CAS  Google Scholar 

  • O’Hagan, S., Dunn, W. B., Brown, M., Knowles, J. D., & Kell, D. B. (2005). Closed-loop, multiobjective optimization of analytical instrumentation: gas chromatography/time-of-flight mass spectrometry of the metabolomes of human serum and of yeast fermentations. Analytical Chemistry, 77, 290–303. doi:10.1021/ac049146x.

    Article  PubMed  CAS  Google Scholar 

  • Odunsi, K., Wollman, R. M., Ambrosone, C. B., Hutson, A., McCann, S. E., Tammela, J., Geisler, J. P., Miller, G., Sellers, T., Cliby, W., Qian, F., Keitz, B., Intengan, M., Lele, S., & Alderfer, J. L. (2005). Detection of epithelial ovarian cancer using 1H-NMR-based metabonomics. International Journal of Cancer, 113, 782–788. doi:10.1002/ijc.20651.

    Article  CAS  Google Scholar 

  • Olanow, C. W., & Tatton, W. G. (1999). Etiology and pathogenesis of Parkinson’s disease. Annual Review of Neuroscience, 22, 123–144. doi:10.1146/annurev.neuro.22.1.123.

    Article  PubMed  CAS  Google Scholar 

  • Parkinson, J. (1817). An essay on the shaking palsy. London: Sherwood, Neely and Jones.

    Google Scholar 

  • Poewe, W., & Wenning, G. (2002). The differential diagnosis of Parkinson’s disease. European Journal of Neurology, 9(Suppl 3), 23–30. doi:10.1046/j.1468-1331.9.s3.3.x.

    Article  PubMed  Google Scholar 

  • Raamsdonk, L. M., Teusink, B., Broadhurst, D., Zhang, N., Hayes, A., Walsh, M. C., Berden, J. A., Brindle, K. M., Kell, D. B., Rowland, J. J., Westerhoff, H. V., van Dam, K., & Oliver, S. G. (2001). A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations. Nature Biotechnology, 19, 45–50. doi:10.1038/83496.

    Article  PubMed  CAS  Google Scholar 

  • Ravasz, E., Somera, A. L., Mongru, D. A., Oltvai, Z. N., & Barabasi, A. L. (2002). Hierarchical organization of modularity in metabolic networks. Science, 297, 1551–1555. doi:10.1126/science.1073374.

    Article  PubMed  CAS  Google Scholar 

  • Sato, S., Mizuno, Y., & Hattori, N. (2005). Urinary 8-hydroxydeoxyguanosine levels as a biomarker for progression of Parkinson disease. Neurology, 64, 1081–1083.

    PubMed  CAS  Google Scholar 

  • Scatton, B., Javoy-Agid, F., Rouquier, L., Dubois, B., & Agid, Y. (1983). Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson’s disease. Brain Research, 275, 321–328. doi:10.1016/0006-8993(83)90993-9.

    Article  PubMed  CAS  Google Scholar 

  • Scherzer, C. R., Eklund, A. C., Morse, L. J., Liao, Z., Locascio, J. J., Fefer, D., Schwarzschild, M. A., Schlossmacher, M. G., Hauser, M. A., Vance, J. M., Sudarsky, L. R., Standaert, D. G., Growdon, J. H., Jensen, R. V., & Gullans, S. R. (2007). Molecular markers of early Parkinson’s disease based on gene expression in blood. Proceedings of the National Academy of Sciences, 104(3), 955–960. doi:10.1073/pnas.0610204104.

    Article  CAS  Google Scholar 

  • Taquet, H., Javoy-Agid, F., Hamon, M., Legrand, J. C., Agid, Y., & Cesselin, F. (1983). Parkinson’s disease affects differently Met5- and Leu5-enkephalin in the human brain. Brain Research, 280, 379–382. doi:10.1016/0006-8993(83)90071-9.

    Article  PubMed  CAS  Google Scholar 

  • Tsuboi, Y., Ahlskog, J. E., Apaydin, H., Parisi, J. E., & Dickson, D. W. (2001). Lewy bodies are not increased in progressive supranuclear palsy compared with normal controls. Neurology, 57, 1675–1678.

    PubMed  CAS  Google Scholar 

  • Underwood, B. R., Broadhurst, D., Dunn, W. B., Ellis, D. I., Michell, A. W., Vacher, C., Mosedale, D. E., Kell, D. B., Barker, R. A., Grainger, D. J., & Rubinsztein, D. C. (2006). Huntington disease patients and transgenic mice have similar pro-catabolic serum metabolite profiles. Brain, 129, 877–886. doi:10.1093/brain/awl027.

    Article  PubMed  Google Scholar 

  • Valafar, F. (2002). Pattern recognition techniques in microarray data analysis: A survey. Annals of the New York Academy of Sciences, 980, 41–64.

    Article  PubMed  CAS  Google Scholar 

  • Van, Q. N., Klose, J. R., Lucas, D. A., Prieto, D. A., Luke, B., Collins, J., Burt, S. K., Chmurny, G. N., Issaq, H. J., Conrads, T. P., Veenstra, T. D., & Keay, S. K. (2003). The use of urine proteomic and metabonomic patterns for the diagnosis of interstitial cystitis and bacterial cystitis. Disease Markers, 19, 169–183.

    PubMed  CAS  Google Scholar 

  • Van der, G. J., & McBurney, R. N. (2005). Innovation: Rescuing drug discovery: In vivo systems pathology and systems pharmacology. Nature Reviews Drug Discovery, 4, 961–967. doi:10.1038/nrd1904.

    Article  CAS  Google Scholar 

  • Vila, M., & Przedborski, S. (2004). Genetic clues to the pathogenesis of Parkinson’s disease. Nature Medicine, 10(Suppl), S58–S62. doi:10.1038/nm1068.

    Article  PubMed  CAS  Google Scholar 

  • Visser, M., Marinus, J., Stiggelbout, A. M., & Van Hilten, J. J. (2004). Assessment of autonomic dysfunction in Parkinson’s disease: The SCOPA-AUT. Movement Disorders, 19, 1306–1312. doi:10.1002/mds.20153.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dave Broadhurst, Rick Dunn, Dave Ellis and Douglas Kell for assistance with the analyses. Funding: DJG is a British Heart Foundation Senior Research Fellow. AWM held a Parkinson’s Disease Society studentship and Sackler award.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Roger A. Barker.

Additional information

David J. Grainger and Roger A. Barker are the senior authors of this manuscript.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Michell, A.W., Mosedale, D., Grainger, D.J. et al. Metabolomic analysis of urine and serum in Parkinson’s disease. Metabolomics 4, 191–201 (2008). https://doi.org/10.1007/s11306-008-0111-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11306-008-0111-9

Keywords

Navigation