Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease

Molecular Neurodegeneration

Omar M. A. El-Agnaf⁴  Wilma D. J. van de Berg⁶  Henk W. Berendse⁸  Charlotte E. Teunissen¹  Takahiko Tokuda³  Bared Safieh-Garabedian⁷  Stephen Poole⁵  Liliana P. Montezinho^1,10  Louise B. Vesterager^1,10  Shiji Varghese²  Mustafa T. Ardah²  Karin D. van Dijk⁶  Nishant N. Vaikath⁹  Nour K. Majbour⁶ 

[1] Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands;Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates;Department of Neurology, Research Institute for Geriatrics, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan;Neurological Disorders Center, Qatar Biomedical Research Institute, and College of Science and Engineering, Hamad Bin Khalifa University (HBKU), Education City, Qatar Foundation, Doha, Qatar;Biotherapeutics Group, National Institute for Biological Standards and Control, Potters Bar, Herts, UK;Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands;College of Medicine, Qatar University, Doha, Qatar;Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands;Neural Plasticity and Repair Unit, Department of Experimental Medical Sciences, Wallenberg Neuroscience Center, BMC A10, Lund University, Lund, Sweden;Department of Neurodegeneration, H. Lundbeck A/S, 2500, Valby, Denmark

关键词: Biomarkers;    Amyloid oligomers;    Cerebrospinal fluid biomarkers;    Alpha synuclein;    Parkinson’s disease;   

Others  :  1235649
DOI  :  10.1186/s13024-016-0072-9

 received in 2015-09-14, accepted in 2016-01-11,  发布年份 2016

【 摘 要 】

Background

Despite decades of intensive research, to date, there is no accepted diagnosis for Parkinson’s disease (PD) based on biochemical analysis of blood or CSF. However, neurodegeneration in the brains of PD patients begins several years before the manifestation of the clinical symptoms, pointing to serious flaw/limitations in this approach.

Results

To explore the potential use of alpha-synuclein (α-syn) species as candidate biomarkers for PD, we generated specific antibodies directed against wide array of α-syn species, namely total-, oligomeric- and phosphorylated-Ser129-α-syn (t-, o- and p-S129-α-syn). Next we sought to employ our antibodies to develop highly specific ELISA assays to quantify α-syn species in biological samples. Finally we verified the usefulness of our assays in CSF samples from 46 PD patients and 48 age-matched healthy controls. We also assessed the discriminating power of combining multiple CSF α-syn species with classical Alzheimer’s disease biomarkers. The combination of CSF o-/t-α-syn, p-S129-α-syn and p-tau provided the best fitting predictive model for discriminating PD patients from controls. Moreover, CSF o-α-syn levels correlated significantly with the severity of PD motor symptoms (r = -0.37).

Conclusion

Our new ELISA assays can serve as research tools to address the unmet need for reliable CSF biomarkers for PD and related disorders.

【 授权许可】

   
2016 Majbour et al.

【 图 表 】

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