title: Longitudinal Measurements of Cerebrospinal Fluid Biomarkers in Parkinson's Disease.
abstract: The purpose of this study was to investigate whether cerebrospinal fluid (CSF) levels of tau, phosphorylated tau, β-amyloid42 , α-synuclein, neurofilament light, and YKL-40 change over time and if changes correlate with motor progression and/or cognitive decline in patients with PD and controls.
  
  
  
  We included 63 patients with PD (nondemented) and 21 neurologically healthy controls from the prospective and longitudinal Swedish BioFINDER study, all of whom had clinical assessments and lumbar punctures at baseline and after 2 years.
  
  
  
  CSF tau levels correlated strongly with α-synuclein. The levels of CSF α-synuclein, tau, phosphorylated tau, neurofilament light, and YKL-40, but not β-amyloid42 , increased in CSF over 2 years in PD. No changes were seen in the control group. Studying patients with a short disease duration ( ≤ 5 years) and patients with a long disease duration ( > 5 years) separately, α-synuclein and tau only increased in the PD group with long disease duration. In the PD group, an increase in phosphorylated tau over 2 years correlated with faster motor progression and faster cognitive decline. An increase in YKL-40 over 2 years correlated with faster cognitive decline.
  
  
  
  CSF biomarkers reflecting Lewy body pathology and neurodegeneration (α-synuclein), neuronal degeneration (tau, phosphorylated tau, and neurofilament light), and inflammation (YKL-40) increase significantly over 2 years in PD. CSF levels of α-synuclein and tau correlate and remain stable in the early symptomatic phase of PD but increase in the later phase. We hypothesize that CSF α-synuclein levels might increase as a result of more intense neurodegeneration in PD with long disease duration. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
authors.affiliation: Department of Neurology, Skåne University Hospital, Malmö, Sweden.|Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Hall
authors.affiliation: Department of Neurology, Skåne University Hospital, Malmö, Sweden.|Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Surova
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg and Mölndal, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Öhrfelt
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg and Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg and Mölndal, Sweden.|University College London Institute of Neurology, London, United Kingdom.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.|Memory Clinic, Skåne University Hospital, Malmö, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D000071451:Chitinase-3-Like Protein 1 / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D010300:Parkinson Disease / Q000134:cerebrospinal fluid*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); C044882:neurofilament protein L; D016875:tau Proteins
keywords: Parkinson's disease; biomarkers; cerebrospinal fluid; longitudinal; prognosis