title: CSF Neurofilament Light Chain but not FLT3 Ligand Discriminates Parkinsonian Disorders.
abstract: The differentiation between multiple system atrophy (MSA) and Parkinson's disease (PD) is difficult, particularly in early disease stages. Therefore, we aimed to evaluate the diagnostic value of neurofilament light chain (NFL), fms-like tyrosine kinase ligand (FLT3L), and total tau protein (t-tau) in cerebrospinal fluid (CSF) as biomarkers to discriminate MSA from PD. Using commercially available enzyme-linked immunosorbent assays, we measured CSF levels of NFL, FLT3L, and t-tau in a discovery cohort of 36 PD patients, 27 MSA patients, and 57 non-neurological controls and in a validation cohort of 32 PD patients, 25 MSA patients, 15 PSP patients, 5 CBS patients, and 56 non-neurological controls. Cut-offs obtained from individual assays and binary logistic regression models developed from combinations of biomarkers were assessed. CSF levels of NFL were substantially increased in MSA and discriminated between MSA and PD with a sensitivity of 74% and specificity of 92% (AUC = 0.85) in the discovery cohort and with 80% sensitivity and 97% specificity (AUC = 0.94) in the validation cohort. FLT3L levels in CSF were significantly lower in both PD and MSA compared to controls in the discovery cohort, but not in the validation cohort. t-tau levels were significantly higher in MSA than PD and controls. Addition of either FLT3L or t-tau to NFL did not improve discrimination of PD from MSA above NFL alone. Our findings show that increased levels of NFL in CSF offer clinically relevant, high accuracy discrimination between PD and MSA.
authors.affiliation: Department of Neurology and Parkinson Center, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre , Nijmegen , Netherlands ; Department of Laboratory Medicine, Radboud University Medical Centre , Nijmegen , Netherlands.
authors.forename: Megan K
authors.initials: MK
authors.lastname: Herbert
authors.affiliation: Department of Neurology and Parkinson Center, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre , Nijmegen , Netherlands ; Parkinson Center , Nijmegen , Netherlands.
authors.forename: Marjolein B
authors.initials: MB
authors.lastname: Aerts
authors.affiliation: Department of Neurology and Parkinson Center, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre , Nijmegen , Netherlands ; Department of Laboratory Medicine, Radboud University Medical Centre , Nijmegen , Netherlands.
authors.forename: Marijke
authors.initials: M
authors.lastname: Beenes
authors.affiliation: UmanDiagnostics , Umeå , Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Norgren
authors.affiliation: Department of Neurology and Parkinson Center, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre , Nijmegen , Netherlands ; Parkinson Center , Nijmegen , Netherlands.
authors.forename: Rianne A J
authors.initials: RA
authors.lastname: Esselink
authors.affiliation: Department of Neurology and Parkinson Center, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre , Nijmegen , Netherlands ; Parkinson Center , Nijmegen , Netherlands.
authors.forename: Bastiaan R
authors.initials: BR
authors.lastname: Bloem
authors.affiliation: Department of Neurology and Parkinson Center, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre , Nijmegen , Netherlands ; Department of Laboratory Medicine, Radboud University Medical Centre , Nijmegen , Netherlands.
authors.forename: H Bea
authors.initials: HB
authors.lastname: Kuiperij
authors.affiliation: Department of Neurology and Parkinson Center, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre , Nijmegen , Netherlands ; Department of Laboratory Medicine, Radboud University Medical Centre , Nijmegen , Netherlands ; Parkinson Center , Nijmegen , Netherlands.
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
keywords: FLT3 ligand; Parkinson’s disease; cerebrospinal fluid; multiple system atrophy; neurofilament light chain