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  • Review Article
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Cerebrospinal fluid biomarkers in Parkinson disease

Nature Reviews Neurology volume 9, pages 131–140 (2013)Cite this article

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Abstract

Clinical diagnosis of Parkinson disease (PD) is difficult in early stages of disease, with high risk of misdiagnosis. The long preclinical phase of PD provides the possibility for early therapeutic intervention once disease-modifying therapies have been developed, but lack of biomarkers for early diagnosis and monitoring of disease progression represents a major obstacle to achievement of this goal. Accordingly, research efforts aimed at identification of novel biomarkers have been increasing in the past 5 years. Cerebrospinal fluid (CSF) is an accessible source of brain-derived proteins, which mirror molecular changes that take place in the CNS. In this Review, we discuss evidence from numerous studies that have focused on identification of candidate CSF biomarkers for PD. Notably, molecular pathways related to α-synuclein, tau and β-amyloid peptides have received considerable attention. CSF levels of the protein DJ-1 are also of interest, although further investigation of this candidate marker is required. These studies support the usefulness of a combination of various CSF biomarkers of PD to increase diagnostic accuracy during early phases of the disease, and to differentiate PD from other neurodegenerative disorders.

Key Points

  • Clinical diagnosis of Parkinson disease (PD) can be difficult at early stages of the disease course

  • Biomarkers for diagnosis and prognosis of PD are not currently available

  • Cerebrospinal fluid levels of α-synuclein, DJ-1, amyloid-β1–42, tau and lysosomal enzymes are promising candidates for PD biomarkers

  • When used alone, these biomarkers have low specificity and sensitivity for PD

  • Combination of several biomarkers that reflect different pathogenic pathways is necessary

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Figure 1: Putative pathogenic pathways underlying CSF biomarkers of PD.

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Acknowledgements

P. Calabresi receives grant support from Ricerca Corrente IRCCS and Ricerca Finalizzata IRCCS (European Community Grant REPLACES). O. El-Agnaf and L. Parnetti have been supported by, and E. Persichetti receives a salary from, the Michael J. Fox Foundation for Parkinson's Disease. D. Chiasserini is supported by the European 7th framework project MEFOPA (Mendelian Forms of Parkinson's disease; EU grant 241791).

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Authors and Affiliations

  1. Clinica Neurologica, Università di Perugia, Ospedale Santa Maria della Misericordia, Santa Andrea delle Fratte, Perugia, 06132, Italy

    Lucilla Parnetti, Anna Castrioto & Nicola Tambasco

  2. Oncoproteomics Laboratory, VUMC, CCA 1-50, VU University Medical Centre, De Boelelaan 1117, Amsterdam, 1081HV, The Netherlands

    Davide Chiasserini

  3. Sezione di Chimica Bromatologica, Biochimica, Fisiologia e Nutrizione, Università di Perugia, Borgo XX Giugno 74, Perugia, 06121, Italy

    Emanuele Persichetti

  4. Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, P. O. Box 17666, Al Ain, UAE

    Omar El-Agnaf

  5. Fondazione Santa Lucia, I.R.C.C.S., Roma, Italy and Clinica Neurologica, Università di Perugia, Ospedale S. Maria della Misericordia, S. Andrea delle Fratte, Perugia, 06132, Italy

    Paolo Calabresi

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  1. Lucilla Parnetti
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  4. Emanuele Persichetti
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  5. Nicola Tambasco
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  6. Omar El-Agnaf
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  7. Paolo Calabresi
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Contributions

L. Parnetti and A. Castrioto researched data for and wrote the article. L. Parnetti, A. Castrioto, D. Chiasserini, E. Persichetti, O. El-Agnaf and P. Calabresi made substantial contributions to discussion of the article content. L. Parnetti, D. Chiasserini, E. Persichetti, N. Tambasco, O. El-Agnaf and P. Calabresi contributed to review and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Lucilla Parnetti.

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Competing interests

A. Castrioto has received travel meeting reimbursement from Novartis. P. Calabresi has received research support from Bayer Schering, Biogen, Boehringer Ingelheim, Lundbeck, Sanofi-Aventis, Sigma-Tau. P. Calabresi, L. Parnetti and O. El-Agnaf have submitted a patent application (UK 1011420.5) for a method for Parkinson disease diagnosis. The other authors declare no competing interests

Supplementary information

Supplementary Table 1

Comparison of two recent studies on use of CSF measurement of α-syn and tau to discriminate PD from controls and other neurodegenerative disorders (DOC 42 kb)

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Parnetti, L., Castrioto, A., Chiasserini, D. et al. Cerebrospinal fluid biomarkers in Parkinson disease. Nat Rev Neurol 9, 131–140 (2013). https://doi.org/10.1038/nrneurol.2013.10

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