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Cerebrospinal fluid biomarkers for the diagnosis and prognosis of Parkinson’s disease: protocol for a systematic review and individual participant data meta-analysis
  1. Paolo Eusebi1,
  2. Oskar Hansson2,3,
  3. Silvia Paciotti1,
  4. Massimiliano Orso4,
  5. Davide Chiasserini1,5,
  6. Paolo Calabresi1,6,
  7. Kaj Blennow7,
  8. Lucilla Parnetti1
  1. 1 Department of Medicine, Neurology Clinic, University of Perugia, Ospedale Santa Maria della Misericordia, Perugia, Perugia, Italy
  2. 2 Department of Clinical Sciences, Clinical Memory Research Unit, Lund University, Lund, Sweden
  3. 3 Memory Clinic, Skåne University Hospital, Malmö, Sweden
  4. 4 Health Planning Service, Department of Epidemiology, Regional Health Authority of Umbria, Perugia, Italy
  5. 5 Oncoproteomics Laboratory, VU University Medical Center, Amsterdam, The Netherlands
  6. 6 Fondazione Santa Lucia, Rome, Italy
  7. 7 Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden
  1. Correspondence to Paolo Eusebi; paoloeusebi{at}


Introduction Idiopathic Parkinson’s disease (PD) is a progressive neurodegenerative disorder related to α-synuclein misfolding and aggregation. For this reason, it belongs to the family of ‘synucleinopathies’, which also includes some other neurological diseases. Although imaging and ancillary investigations may be helpful in the diagnostic workup, the diagnosis of PD mostly relies on the clinician’s expertise. Furthermore, there is a need today for markers that can track the disease progression in PD that might improve the evaluation of novel disease-modifying therapies. The cerebrospinal fluid (CSF) has been widely investigated with the purpose of finding useful diagnostic and prognostic biomarkers for PD.

Methods and analysis This systematic review protocol has been developed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocol 2015 statement and was registered on the PROSPERO international prospective register of systematic reviews. An international collaboration will be established. We will search the Cochrane Library, Web of Science, Medline and Embase from inception, using appropriate search strategies. Individual participant data from all included studies will be merged into a single database. We will include any study assessing the diagnostic and prognostic role of CSF biomarkers in PD. To evaluate the risk of bias and applicability of primary diagnostic accuracy studies, we will use Quality Assessment of Diagnostic Accuracy Studies-2 and Quality in Prognostic Studies. We will use standard meta-analytic procedures. We will first explore the utility of each CSF biomarker in turn. For each biomarker, we will assess its diagnostic and prognostic utility by means of receiver operating characteristic analysis and regression models. We will then move towards a multivariate approach considering different panels of biomarkers.

Ethics and dissemination Our study will not include confidential data, and no intervention will be involved, so ethical approval is not required. The results of the study will be reported in international peer-reviewed journals.

  • Parkinson’s disease
  • cerebrospinal fluid
  • meta-analysis
  • diagnosis
  • prognosis

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  • Contributors PE: conceived the idea, and planned and designed the study protocol. PE and LP: wrote the first draft. MO: designed the search strategy and planned the data extraction. PE: planned the data extraction and statistical analysis. PC, OH and KB: provided critical insights. All authors: approved and contributed to the final written manuscript.

  • Funding This project is funded by the Italian Ministry of Health (Grant ID: GR-2013-02357757).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.