Diagnostic utility of CSF α-synuclein species in Parkinson's disease: protocol for a systematic review and meta-analysis.
The diagnostic criteria currently used for Parkinson's disease (PD) are mainly based on clinical motor symptoms. For these reasons many biomarkers are under investigation to support the diagnosis at the early stage. The neuropathological hallmark of PD is represented by Lewy bodies (LBs), which are intracytoplasmic inclusions in substantia nigra neurons. The major component of LBs, α-synuclein (α-syn), has been implicated in the pathogenesis of PD and in other 'synucleinopathies' such as multisystem atrophy (MSA) and dementia with LBs (DLBs). Several studies have investigated this presynaptic protein as a potential biomarker of PD. The aim of our meta-analysis is to determine the ability of cerebrospinal fluid (CSF) concentrations of total α-syn, oligomeric α-syn and phosphorylated α-syn to discriminate patients with PD from healthy participants, non-degenerative neurological controls and patients suffering from parkinsonism and or synucleinopathies.



This systematic review protocol has been developed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocol (PRISMA-P) 2015 statement and was registered on PROSPERO (CRD42016013217). We will search Cochrane Library, Web of Science, MEDLINE (via PubMed) and EMBASE from inception, using appropriate search strategies. Two independent reviewers will screen titles, abstracts and full-text articles, and will complete data abstraction. We will include studies that involved patients with PD, DLB, MSA, progressive supranuclear palsy, corticobasal disease and vascular PD, and in which at least one between total α-syn, oligomeric α-syn and phosphorylated α-syn was measured in CSF. To evaluate the risk of bias and applicability of primary diagnostic accuracy studies, we will use QUADAS-2.



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.
Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy Health Planning Service, Department of Epidemiology, Regional Health Authority of Umbria, Perugia, Italy.
Paolo
P
Eusebi
Neurology Unit, Department of Specialist Medicine, USL Umbria 1 North Area, Gubbio and Gualdo Tadino Hospital, Gubbio, Italy.
David
D
Giannandrea
Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy.
Leonardo
L
Biscetti
Health Planning Service, Department of Epidemiology, Regional Health Authority of Umbria, Perugia, Italy.
Iosief
I
Abraha
Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy.
Davide
D
Chiasserini
Health Planning Service, Department of Epidemiology, Regional Health Authority of Umbria, Perugia, Italy.
Massimiliano
M
Orso
Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy IRCCS Fondazione Santa Lucia, Rome, Italy.
Paolo
P
Calabresi
Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy.
Lucilla
L
Parnetti
D015415:Biomarkers / Q000134:cerebrospinal fluid; D003937:Diagnosis, Differential; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D019578:Multiple System Atrophy; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D012107:Research Design; D000078202:Systematic Reviews as Topic; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*; D015201:Meta-Analysis as Topic
D015415:Biomarkers; D051844:alpha-Synuclein
diagnostics; meta-analysis; systematic review; α-synuclein