title: Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson's disease.
abstract: 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).
  
  
  CONCLUSIONS
  Our new ELISA assays can serve as research tools to address the unmet need for reliable CSF biomarkers for PD and related disorders.
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.|Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Nour K
authors.initials: NK
authors.lastname: Majbour
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.|Neural Plasticity and Repair Unit, Department of Experimental Medical Sciences, Wallenberg Neuroscience Center, BMC A10, Lund University, Lund, Sweden.
authors.forename: Nishant N
authors.initials: NN
authors.lastname: Vaikath
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Karin D
authors.initials: KD
authors.lastname: van Dijk
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Mustafa T
authors.initials: MT
authors.lastname: Ardah
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Shiji
authors.initials: S
authors.lastname: Varghese
authors.affiliation: Department of Neurodegeneration, H. Lundbeck A/S, 2500, Valby, Denmark.
authors.forename: Louise B
authors.initials: LB
authors.lastname: Vesterager
authors.affiliation: Department of Neurodegeneration, H. Lundbeck A/S, 2500, Valby, Denmark.
authors.forename: Liliana P
authors.initials: LP
authors.lastname: Montezinho
authors.affiliation: Biotherapeutics Group, National Institute for Biological Standards and Control, Potters Bar, Herts, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Poole
authors.affiliation: College of Medicine, Qatar University, Doha, Qatar.
authors.forename: Bared
authors.initials: B
authors.lastname: Safieh-Garabedian
authors.affiliation: Department of Neurology, Research Institute for Geriatrics, Kyoto Prefectural University of Medicine, Kyoto, 602-0841, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tokuda
authors.affiliation: Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.affiliation: Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Henk W
authors.initials: HW
authors.lastname: Berendse
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Wilma D J
authors.initials: WD
authors.lastname: van de Berg
authors.affiliation: Neurological Disorders Center, Qatar Biomedical Research Institute, and College of Science and Engineering, Hamad Bin Khalifa University (HBKU), Education City, Qatar Foundation, P.O. Box 5825, Doha, Qatar. oelagnaf@qf.org.qa.
authors.forename: Omar M A
authors.initials: OM
authors.lastname: El-Agnaf
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D010766:Phosphorylation; D055503:Protein Multimerization; D051844:alpha-Synuclein / Q000097:blood / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D051844:alpha-Synuclein; D016875:tau Proteins