title: CSF biomarkers and clinical progression of Parkinson disease.
abstract: OBJECTIVE
  To investigate whether certain CSF biomarkers at baseline can predict future progression of motor symptoms and cognitive decline in patients with Parkinson disease (PD).
  
  
  METHODS
  Patients and controls were recruited from hospitals in southern Sweden as part of the prospective and longitudinal Swedish BioFinder Study. In the present study, we included 42 patients with PD and 69 controls who had clinical assessment and lumbar puncture at baseline. Baseline CSF samples were analyzed for α-synuclein (αSyn), β-amyloid 1-42 (Aβ42), tau, phosphorylated tau, and neurofilament light. Associations between CSF markers at baseline and change in clinical characteristics after 2 years of follow-up were investigated using multivariate models adjusting for age, sex, disease duration, and levodopa-equivalent daily dose.
  
  
  RESULTS
  Higher levels of αSyn within the PD group were associated with progression of motor symptoms and cognitive decline over 2 years, indicated by significant relationships between αSyn and change in Hoehn and Yahr (β = 0.394, p = 0.043), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (β = 0.449, p = 0.013), Timed Up and Go (β = 0.406, p = 0.023), and A Quick Test of Cognitive Speed (β = 0.423, p = 0.018). Lower levels of Aβ42 were associated with worsening of performance on delayed memory recall (F = 5.834, p = 0.022). Finally, high levels of phosphorylated tau were associated with worsening in motor symptoms (UPDRS-III, β = 0.350, p = 0.045; Hoehn and Yahr, β = 0.366, p = 0.038).
  
  
  CONCLUSIONS
  We found evidence of a link between higher levels of αSyn at baseline and worsening of motor symptoms and cognitive speed over 2 years in PD. Increased αSyn might be a marker of more intense synaptic degeneration in PD. The results indicate that cortical amyloid pathology (low CSF Aβ42) is associated with memory decline.
authors.affiliation: From the Department of Neurology (S.H., Y.S.) and Memory Clinic (O.H.), Skåne University Hospital; Department of Clinical Sciences (S.H., Y.S., D.L., O.H.), Lund University; Department of Psychiatry and Neurochemistry (A.O., H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg and Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and Psychiatry Skåne (D.L.), Lund, Sweden. Sara.Hall@med.lu.se Oskar.Hansson@med.lu.se.
authors.forename: Sara
authors.initials: S
authors.lastname: Hall
authors.affiliation: From the Department of Neurology (S.H., Y.S.) and Memory Clinic (O.H.), Skåne University Hospital; Department of Clinical Sciences (S.H., Y.S., D.L., O.H.), Lund University; Department of Psychiatry and Neurochemistry (A.O., H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg and Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and Psychiatry Skåne (D.L.), Lund, Sweden.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Surova
authors.affiliation: From the Department of Neurology (S.H., Y.S.) and Memory Clinic (O.H.), Skåne University Hospital; Department of Clinical Sciences (S.H., Y.S., D.L., O.H.), Lund University; Department of Psychiatry and Neurochemistry (A.O., H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg and Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and Psychiatry Skåne (D.L.), Lund, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Öhrfelt
authors.affiliation: From the Department of Neurology (S.H., Y.S.) and Memory Clinic (O.H.), Skåne University Hospital; Department of Clinical Sciences (S.H., Y.S., D.L., O.H.), Lund University; Department of Psychiatry and Neurochemistry (A.O., H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg and Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and Psychiatry Skåne (D.L.), Lund, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: From the Department of Neurology (S.H., Y.S.) and Memory Clinic (O.H.), Skåne University Hospital; Department of Clinical Sciences (S.H., Y.S., D.L., O.H.), Lund University; Department of Psychiatry and Neurochemistry (A.O., H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg and Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and Psychiatry Skåne (D.L.), Lund, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindqvist
authors.affiliation: From the Department of Neurology (S.H., Y.S.) and Memory Clinic (O.H.), Skåne University Hospital; Department of Clinical Sciences (S.H., Y.S., D.L., O.H.), Lund University; Department of Psychiatry and Neurochemistry (A.O., H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg and Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and Psychiatry Skåne (D.L.), Lund, 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; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000503:physiopathology; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000503:physiopathology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D011379:Prognosis; D011446:Prospective Studies; D013548:Sweden; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); C044882:neurofilament protein L; D016875:tau Proteins