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Mov Disord. 2017 Aug;32(8):1117-1130. doi: 10.1002/mds.27090. Epub 2017 Jul 22.

A user's guide for α-synuclein biomarker studies in biological fluids: Perianalytical considerations.

Author information

1
Paracelsus-Elena-Klinik, Kassel, Germany.
2
Department of Neurology, University Medical Center, Göttingen, Germany.
3
Roche Diagnostics International Ltd, Rotkreuz, Switzerland.
4
Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), and College of Science and Engineering, HBKU, Education City, Qatar Foundation, Doha, Qatar.
5
University of San Diego, San Diego, California, USA.
6
Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Faculty of Life Science, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland.
7
Northwestern University School of Medicine, Chicago, Illinois, USA.
8
Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
9
Center for Neurodegenerative Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
10
MesoScale Discovery, Gaithersburg, Maryland, USA.
11
ADx NeuroSciences, Gent, Belgium.
12
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, UK.
13
University of Washington, Seattle, Washington, USA.
14
Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
15
Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
16
BioLegend, Dedham, Massachusetts, USA.

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.

KEYWORDS:

Biomarker; Parkinson's disease; cerebrospinal fluid; diagnostics; standard operating procedures; α-synuclein

PMID:
28734051
PMCID:
PMC5638072
DOI:
10.1002/mds.27090
[Indexed for MEDLINE]
Free PMC Article

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