The Utility of α-Synuclein as Biofluid Marker in Neurodegenerative Diseases: a Systematic Review of The Literature

Abstract

The discovery of α-synuclein (α-syn) as a major component of Lewy bodies, neuropathological hallmark of Parkinson’s disease (PD), dementia with Lewy bodies and of glial inclusions in multiple system atrophy initiated the investigation of α-syn as a biomarker in cerebrospinal fluid (CSF). Due to the involvement of the periphery in PD the quantification of α-syn in peripheral fluids such as serum, plasma and saliva has been investigated as well. We review how the development of multiple assays for the quantification of α-syn has yielded novel insights into the variety of α-syn species present in the different fluids; the optimal preanalytical conditions required for robust quantification and the potential clinical value of α-syn as biomarker. We also suggest future approaches to use of CSF α-syn in neurodegenerative diseases.

Keywords::

• α-synuclein
• biomarker
• CSF
• diagnosis
• ELISA
• Parkinson’s disease

Financial & competing interests disclosure

This is an EU Joint Programme–Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND–www.jpnd.eu: Denmark (Innovation Fund Denmark); Finland (Academy of Finland, Research Council for Health); Germany (BMBF); Italy (Finanziamento Ministero Salute); The Netherlands: (ZonMw); S Engelborghs is supported by the University of Antwerp Research Fund and the Alzheimer Research Foundation (SAO-FRA). This research has also been co-financed by ERDF (European Regional Development Fund) and Greek national funds through the Operational Program ‘Competitiveness and Entrepreneurship’ of the NSRF (National Strategic Reference Framework); reek national funds through the Operational Program ‘Competitiveness and Entrepreneurship’ of the NSRF (National Strategic Reference Framework). S Engelborghs was/is consultant for Innogenetics/Fujirebio Europe and Roche diagnostics. I Rektorova is supported by the project ‘CEITEC–Central European Institute of Technology’ (CZ.1.05/1.100.02.0068) from the European Regional Development Fund. E Vanmechelen is a co-founder of ADx NeuroSciences. MM Verbeek served on an advisory board for Roche. B Mollenhauer has received independent research grants from TEVA-Pharma, Desitin, Boehringer Ingelheim, GE Healthcare and honoraria for consultancy from Bayer Schering Pharma AG, Roche, AbbVie, TEVA-Pharma, for presentations from GlaxoSmithKline, Orion Pharma, TEVA-Pharma and travel costs from TEVA-Pharma. B Mollenhauer is member of the executive steering committee of the Parkinson Progression Marker Initiative of the Michael J. Fox Foundation for Parkinson’s Research and has received grants from the BMBF, EU, Deutsche Parkinson Vereinigung, Michael J. Fox Foundation for Parkinson’s Research, Stifterverband für die deutsche Wissenschaft, and has scientific collaborations with Roche, Ely Lilly, BioLegend and Biogen Idec. B Mollenhauer is listed as co-inventors in a patent application to the US Patent Office related to the quantification of α-synuclein in biological fluids for the purpose of improved diagnosis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This is an EU Joint Programme–Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND–www.jpnd.eu: Denmark (Innovation Fund Denmark); Finland (Academy of Finland, Research Council for Health); Germany (BMBF); Italy (Finanziamento Ministero Salute); The Netherlands: (ZonMw); S Engelborghs is supported by the University of Antwerp Research Fund and the Alzheimer Research Foundation (SAO-FRA). This research has also been co-financed by ERDF (European Regional Development Fund) and Greek national funds through the Operational Program ‘Competitiveness and Entrepreneurship’ of the NSRF (National Strategic Reference Framework); reek national funds through the Operational Program ‘Competitiveness and Entrepreneurship’ of the NSRF (National Strategic Reference Framework). S Engelborghs was/is consultant for Innogenetics/Fujirebio Europe and Roche diagnostics. I Rektorova is supported by the project ‘CEITEC–Central European Institute of Technology’ (CZ.1.05/1.100.02.0068) from the European Regional Development Fund. E Vanmechelen is a co-founder of ADx NeuroSciences. MM Verbeek served on an advisory board for Roche. B Mollenhauer has received independent research grants from TEVA-Pharma, Desitin, Boehringer Ingelheim, GE Healthcare and honoraria for consultancy from Bayer Schering Pharma AG, Roche, AbbVie, TEVA-Pharma, for presentations from GlaxoSmithKline, Orion Pharma, TEVA-Pharma and travel costs from TEVA-Pharma. B Mollenhauer is member of the executive steering committee of the Parkinson Progression Marker Initiative of the Michael J. Fox Foundation for Parkinson’s Research and has received grants from the BMBF, EU, Deutsche Parkinson Vereinigung, Michael J. Fox Foundation for Parkinson’s Research, Stifterverband für die deutsche Wissenschaft, and has scientific collaborations with Roche, Ely Lilly, BioLegend and Biogen Idec. B Mollenhauer is listed as co-inventors in a patent application to the US Patent Office related to the quantification of α-synuclein in biological fluids for the purpose of improved diagnosis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.