title: Longitudinal changes in CSF alpha-synuclein species reflect Parkinson's disease progression.
abstract: Parkinson's disease (PD) diagnosis is mainly based on clinical criteria, with a high risk of misdiagnosis. The identification of reliable biomarkers for disease diagnosis and progression has a key role for developing disease-modifying therapies. In this article, we investigated the longitudinal changes of CSF α-synuclein species in early PD patients and explored the potential use of these species as surrogate biomarkers for PD progression.
  
  
  
  We used our newly developed enzyme-linked immunosorbent assay systems for measuring different forms of α-synuclein, such as oligomeric-α-synuclein, phosphorylated-α-synuclein at serine 129, or total-α-synuclein in CSF from the longitudinal Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study cohort (n = 121). CSF Alzheimer's disease biomarkers (total-tau, phosphorylated-tau, Aβ40, and Aβ42) were also measured for this cohort.
  
  
  
  Interestingly, total-α-synuclein and oligomeric-α-synuclein levels significantly increased during the 2-year Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study follow-up period, whereas phosphorylated-α-synuclein at serine 129 levels showed a longitudinal decrease. We have also noted an association between a change of the oligomeric-α-synuclein/total-α-synuclein ratio and a worsening of motor signs, in particular in the postural-instability and gait-difficulty dominant PD group. A strong positive correlation between the changes in CSF total-α-synuclein and oligomeric-α-synuclein during the 2-year Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study was also noted (r = 0.84, P < .001).
  
  
  
  Our data show that CSF α-synuclein species have a dynamic pattern along the course of the disease, supporting their possible role as progression biomarkers for PD and their link with PD clinical phenotypes. © 2016 International Parkinson and Movement Disorder Society.
authors.affiliation: Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, PO Box 5825, Doha, Qatar.|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: Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, PO Box 5825, Doha, Qatar.|Neural Plasticity and Repair Unit, Department of Experimental Medical Sciences, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
authors.forename: Nishant N
authors.initials: NN
authors.lastname: Vaikath
authors.affiliation: Dipartimento di Medicina, Sezione di Neurologia, Università degli Studi di Perugia, Perugia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Eusebi
authors.affiliation: Dipartimento di Medicina, Sezione di Neurologia, Università degli Studi di Perugia, Perugia, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Chiasserini
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Mustafa
authors.initials: M
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 Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: M Emdadul
authors.initials: ME
authors.lastname: Haque
authors.affiliation: Department of Neurology, Research Institute for Geriatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tokuda
authors.affiliation: Department of Neurology, Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: Peggy
authors.initials: P
authors.lastname: Auinger
authors.affiliation: Dipartimento di Medicina, Sezione di Neurologia, Università degli Studi di Perugia, Perugia, Italy.|IRCCS - S. Lucia Foundation, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
authors.affiliation: Dipartimento di Medicina, Sezione di Neurologia, Università degli Studi di Perugia, Perugia, Italy.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Parnetti
authors.affiliation: Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, PO Box 5825, Doha, Qatar. oelagnaf@qf.org.qa.|Life Sciences Division, College of Science and Engineering, Hamad Bin Khalifa University (HBKU), Education City, Qatar Foundation, PO Box 5825, Doha, Qatar. oelagnaf@qf.org.qa.
authors.forename: Omar M A
authors.initials: OM
authors.lastname: El-Agnaf
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use; D015415:Biomarkers / Q000134:cerebrospinal fluid; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D051844:alpha-Synuclein
keywords: DATATOP; Parkinson's disease; alpha-synuclein; biomarkers; oligomers