Journal article
A user's guide for α-synuclein biomarker studies in biological fluids: Perianalytical considerations
Movement disorders, Vol.32(8), pp.1117-1130
08/2017
DOI: 10.1002/mds.27090
PMCID: PMC5638072
PMID: 28734051
Abstract
Parkinson's disease biomarkers are needed to increase diagnostic accuracy, to objectively monitor disease progression and to assess therapeutic efficacy as well as target engagement when evaluating novel drug and therapeutic strategies. This article summarizes perianalytical considerations for biomarker studies (based on immunoassays) in Parkinson's disease, with emphasis on quantifying total α-synuclein protein in biological fluids. Current knowledge and pitfalls are discussed, and selected perianalytical variables are presented systematically, including different temperature of sample collection and types of collection tubes, gradient sampling, the addition of detergent, aliquot volume, the freezing time, and the different thawing methods. We also discuss analytical confounders. We identify gaps in the knowledge and delineate specific areas that require further investigation, such as the need to identify posttranslational modifications of α-synuclein and antibody-independent reference methods for quantification, as well as the analysis of potential confounders, such as comorbidities, medication, and phenotypes of Parkinson's disease in larger cohorts. This review could be used as a guideline for future Parkinson's disease biomarker studies and will require regular updating as more information arises in this growing field, including new technical developments as they become available. In addition to reviewing best practices, we also identify the current technical limitations and gaps in the knowledge that should be addressed to enable accurate and quantitative assessment of α-synuclein levels in the clinical setting. © 2017 International Parkinson and Movement Disorder Society.
Details
- Title: Subtitle
- A user's guide for α-synuclein biomarker studies in biological fluids: Perianalytical considerations
- Creators
- Brit Mollenhauer - Department of Neurology, University Medical Center, Göttingen, GermanyRichard Batrla - Roche Diagnostics International Ltd, Rotkreuz, SwitzerlandOmar El-Agnaf - Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), and College of Science and Engineering, HBKU, Education City, Qatar Foundation, Doha, QatarDouglas R Galasko - University of San Diego, San Diego, California, USAHilal A Lashuel - Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Faculty of Life Science, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, SwitzerlandKalpana M Merchant - Northwestern University School of Medicine, Chicago, Illinois, USALesley M Shaw - Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, Pennsylvania, USADennis J Selkoe - Center for Neurodegenerative Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USARobert Umek - MesoScale Discovery, Gaithersburg, Maryland, USAHugo Vanderstichele - ADx NeuroSciences, Gent, BelgiumHenrik Zetterberg - Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; UK Dementia Research Institute, London, UKJing Zhang - University of Washington, Seattle, Washington, USAChelsea Caspell-Garcia - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USAChris Coffey - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USASamantha J Hutten - Michael J. Fox Foundation for Parkinson's Research, New York, New York, USAMark Frasier - Michael J. Fox Foundation for Parkinson's Research, New York, New York, USAPeggy Taylor - BioLegend, Dedham, Massachusetts, USAInvestigating Synuclein Consortium of the Michael J. Fox Foundation for Parkinson's Research
- Resource Type
- Journal article
- Publication Details
- Movement disorders, Vol.32(8), pp.1117-1130
- Publisher
- United States
- DOI
- 10.1002/mds.27090
- PMID
- 28734051
- PMCID
- PMC5638072
- ISSN
- 0885-3185
- eISSN
- 1531-8257
- Grant note
- RF1 NS083845 / NINDS NIH HHS P50 AG005131 / NIA NIH HHS
- Language
- English
- Date published
- 08/2017
- Academic Unit
- Biostatistics
- Record Identifier
- 9983997326502771
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