Diagnostic utility of cerebrospinal fluid α-synuclein in Parkinson's disease: A systematic review and meta-analysis

Paolo Eusebi, David Giannandrea, Leonardo Biscetti, Iosief Abraha, Davide Chiasserini, Massimiliano Orso, Paolo Calabresi, Lucilla Parnetti

Research output: Contribution to journalArticle

Abstract

Background: The accumulation of misfolded α-synuclein aggregates is associated with PD. However, the diagnostic value of the α-synuclein levels in CSF is still under investigation. Methods: A comprehensive search of the literature was performed, yielding 34 studies eligible for meta-analysis. We included studies that reported data on CSF total, oligomeric and phosphorylated α-synuclein in patients with PD and healthy participants, neurological controls, or other parkinsonisms. Standardized mean differences were pooled using random-effects models, and heterogeneity was reported as I2. Bivariate random effects meta-analysis was also performed on diagnostic data. Methodological quality of the selected studies was assessed using the QUADAS-2 tool. Results: Concentrations of α-synuclein species in PD did not show significant differences with respect to the levels found in other parkinsonisms. Total α-synuclein was significantly reduced in PD when compared with controls (standardized mean differences −0.48; P <.001, I2 = 60%). Oligomeric (standardized mean differences 0.57; P <.001, I2 = 44%) and phosphorylated α-synuclein (standardized mean differences 0.86; P <.001) were significantly increased in PD when compared with controls. Sensitivity and specificity for distinguishing PD and controls were 0.72 and 0.65, respectively, for total α-synuclein, and 0.71 and 0.64, respectively, for oligomeric α-syn. Conclusion: Most of the studies were at high risk of bias and have concerns regarding applicability. Diagnostic performance of CSF α-synuclein species is still below what would be considered acceptable for their introduction in clinical practice. Future research should focus on combining α-synuclein species with other biochemical markers as well on improving the standardization of current assays.

Original languageEnglish
Pages (from-to)1389-1400
Number of pages12
JournalMovement Disorders
Volume32
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

Keywords

  • alpha-synuclein
  • biomarker
  • cerebrospinal fluid
  • meta-analysis
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Eusebi, P., Giannandrea, D., Biscetti, L., Abraha, I., Chiasserini, D., Orso, M., Calabresi, P., & Parnetti, L. (2017). Diagnostic utility of cerebrospinal fluid α-synuclein in Parkinson's disease: A systematic review and meta-analysis. Movement Disorders, 32(10), 1389-1400. https://doi.org/10.1002/mds.27110