title: Fluid biomarkers in multiple system atrophy: A review of the MSA Biomarker Initiative.
abstract: Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results suggest that combining several CSF fluid biomarkers may be more successful than using single markers, at least for the diagnosis. Currently, the clinically most useful markers may comprise a combination of the light chain of neurofilament (which is consistently elevated in MSA compared to controls and Parkinson's disease), metabolites of the catecholamine pathway and proteins such as α-synuclein, DJ-1 and total-tau. Beyond future efforts in biomarker discovery, the harmonization of standard operating procedures will be crucial for future success.
authors.affiliation: Service de Neurologie, CHU de Bordeaux, F-33076 Bordeaux, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Laurens
authors.affiliation: Department of Neurology, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden.
authors.forename: Radu
authors.initials: R
authors.lastname: Constantinescu
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston.
authors.forename: Roy
authors.initials: R
authors.lastname: Freeman
authors.affiliation: Institute of Brain Behaviour and Mental Heath, University of Manchester, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gerhard
authors.affiliation: Institute of Clinical Neurobiology, Kenyongasse 18, A-1070 Vienna, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Jellinger
authors.affiliation: Quanterix, Inc., Lexington, MA 021421, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jeromin
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Krismer
authors.affiliation: Paracelsus-Elena-Klinik, Kassel, Germany and Department of Neuropathology, University Medical Center Goettingen, Germany.
authors.forename: Brit
authors.initials: B
authors.lastname: Mollenhauer
authors.affiliation: Program in Neuroscience, The Ottawa Hospital, University of Ottawa Brain and Mind Research Institute, Ottawa, Ontario, Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Schlossmacher
authors.affiliation: Perelman School of Medicine, University of Pennsylvania.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.affiliation: Department of Neurology, Parkinson Center, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands; Department of Laboratory Medicine, Parkinson Center, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Gregor K
authors.initials: GK
authors.lastname: Wenning
authors.affiliation: Department of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Winge
authors.affiliation: Department of Pathology, University of WA, Seattle, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Service de Neurologie, CHU de Bordeaux, F-33076 Bordeaux, France; Centre de référence atrophie multisystématisée, CHU de Bordeaux, F-33076 Bordeaux, France; Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33076 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33076 Bordeaux, France. Electronic address: wassilios.meissner@chu-bordeaux.fr.
authors.forename: Wassilios G
authors.initials: WG
authors.lastname: Meissner
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood* / Q000134:cerebrospinal fluid*; D001921:Brain / Q000378:metabolism; D002395:Catecholamines / Q000032:analysis; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism; D019578:Multiple System Atrophy / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D009410:Nerve Degeneration / Q000378:metabolism; D051844:alpha-Synuclein / Q000032:analysis
chemical_list: D015415:Biomarkers; D002395:Catecholamines; D051844:alpha-Synuclein
keywords: Blood; Cerebrospinal fluid; Glia; Multiple system atrophy; Tau; α-synuclein