Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder.
OBJECTIVE
To determine if blood neurofilament light chain (NfL) protein can discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with equally high diagnostic accuracy as CSF NfL, and can therefore improve the diagnostic workup of parkinsonian disorders.


METHODS
The study included 3 independent prospective cohorts: the Lund (n = 278) and London (n = 117) cohorts, comprising healthy controls and patients with PD, progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), as well as an early disease cohort (n = 109) of patients with PD, PSP, MSA, or CBS with disease duration ≤3 years. Blood NfL concentration was measured using an ultrasensitive single molecule array (Simoa) method, and the diagnostic accuracy to distinguish PD from APD was investigated.


RESULTS
We found strong correlations between blood and CSF concentrations of NfL (ρ ≥ 0.73-0.84,p≤ 0.001). Blood NfL was increased in patients with MSA, PSP, and CBS (i.e., all APD groups) when compared to patients with PD as well as healthy controls in all cohorts (p< 0.001). Furthermore, in the Lund cohort, blood NfL could accurately distinguish PD from APD (area under the curve [AUC] 0.91) with similar results in both the London cohort (AUC 0.85) and the early disease cohort (AUC 0.81).


CONCLUSIONS
Quantification of blood NfL concentration can be used to distinguish PD from APD. Blood-based NfL might consequently be included in the diagnostic workup of patients with parkinsonian symptoms in both primary care and specialized clinics.


METHODS
This study provides Class III evidence that blood NfL levels discriminate between PD and APD.
From the Clinical Memory Research Unit (O.H., S.J., S.H.), Department of Clinical Sciences, Lund University; Memory Clinic (O.H., S.J., S.H.), Skåne University Hospital, Sweden; UCL Institute of Neurology (N.M., A.J.L., H.Z.), Queen Square, London, UK; Clinical Neurochemistry Laboratory (R.C., H.Z., K.B.), Institute of Neuroscience and Physiology (U.A.), The Sahlgrenska Academy at University of Gothenburg, Mölndal; UmanDiagnostics (N.N.), Umeå; and Department of Pharmacology and Clinical Neuroscience (J.L., L.F.), Umeå University, Sweden. Oskar.Hansson@med.lu.se.
Oskar
O
Hansson
From the Clinical Memory Research Unit (O.H., S.J., S.H.), Department of Clinical Sciences, Lund University; Memory Clinic (O.H., S.J., S.H.), Skåne University Hospital, Sweden; UCL Institute of Neurology (N.M., A.J.L., H.Z.), Queen Square, London, UK; Clinical Neurochemistry Laboratory (R.C., H.Z., K.B.), Institute of Neuroscience and Physiology (U.A.), The Sahlgrenska Academy at University of Gothenburg, Mölndal; UmanDiagnostics (N.N.), Umeå; and Department of Pharmacology and Clinical Neuroscience (J.L., L.F.), Umeå University, Sweden.
Shorena
S
Janelidze
From the Clinical Memory Research Unit (O.H., S.J., S.H.), Department of Clinical Sciences, Lund University; Memory Clinic (O.H., S.J., S.H.), Skåne University Hospital, Sweden; UCL Institute of Neurology (N.M., A.J.L., H.Z.), Queen Square, London, UK; Clinical Neurochemistry Laboratory (R.C., H.Z., K.B.), Institute of Neuroscience and Physiology (U.A.), The Sahlgrenska Academy at University of Gothenburg, Mölndal; UmanDiagnostics (N.N.), Umeå; and Department of Pharmacology and Clinical Neuroscience (J.L., L.F.), Umeå University, Sweden.
Sara
S
Hall
From the Clinical Memory Research Unit (O.H., S.J., S.H.), Department of Clinical Sciences, Lund University; Memory Clinic (O.H., S.J., S.H.), Skåne University Hospital, Sweden; UCL Institute of Neurology (N.M., A.J.L., H.Z.), Queen Square, London, UK; Clinical Neurochemistry Laboratory (R.C., H.Z., K.B.), Institute of Neuroscience and Physiology (U.A.), The Sahlgrenska Academy at University of Gothenburg, Mölndal; UmanDiagnostics (N.N.), Umeå; and Department of Pharmacology and Clinical Neuroscience (J.L., L.F.), Umeå University, Sweden.
Nadia
N
Magdalinou
From the Clinical Memory Research Unit (O.H., S.J., S.H.), Department of Clinical Sciences, Lund University; Memory Clinic (O.H., S.J., S.H.), Skåne University Hospital, Sweden; UCL Institute of Neurology (N.M., A.J.L., H.Z.), Queen Square, London, UK; Clinical Neurochemistry Laboratory (R.C., H.Z., K.B.), Institute of Neuroscience and Physiology (U.A.), The Sahlgrenska Academy at University of Gothenburg, Mölndal; UmanDiagnostics (N.N.), Umeå; and Department of Pharmacology and Clinical Neuroscience (J.L., L.F.), Umeå University, Sweden.
Andrew J
AJ
Lees
From the Clinical Memory Research Unit (O.H., S.J., S.H.), Department of Clinical Sciences, Lund University; Memory Clinic (O.H., S.J., S.H.), Skåne University Hospital, Sweden; UCL Institute of Neurology (N.M., A.J.L., H.Z.), Queen Square, London, UK; Clinical Neurochemistry Laboratory (R.C., H.Z., K.B.), Institute of Neuroscience and Physiology (U.A.), The Sahlgrenska Academy at University of Gothenburg, Mölndal; UmanDiagnostics (N.N.), Umeå; and Department of Pharmacology and Clinical Neuroscience (J.L., L.F.), Umeå University, Sweden.
Ulf
U
Andreasson
From the Clinical Memory Research Unit (O.H., S.J., S.H.), Department of Clinical Sciences, Lund University; Memory Clinic (O.H., S.J., S.H.), Skåne University Hospital, Sweden; UCL Institute of Neurology (N.M., A.J.L., H.Z.), Queen Square, London, UK; Clinical Neurochemistry Laboratory (R.C., H.Z., K.B.), Institute of Neuroscience and Physiology (U.A.), The Sahlgrenska Academy at University of Gothenburg, Mölndal; UmanDiagnostics (N.N.), Umeå; and Department of Pharmacology and Clinical Neuroscience (J.L., L.F.), Umeå University, Sweden.
Niklas
N
Norgren
From the Clinical Memory Research Unit (O.H., S.J., S.H.), Department of Clinical Sciences, Lund University; Memory Clinic (O.H., S.J., S.H.), Skåne University Hospital, Sweden; UCL Institute of Neurology (N.M., A.J.L., H.Z.), Queen Square, London, UK; Clinical Neurochemistry Laboratory (R.C., H.Z., K.B.), Institute of Neuroscience and Physiology (U.A.), The Sahlgrenska Academy at University of Gothenburg, Mölndal; UmanDiagnostics (N.N.), Umeå; and Department of Pharmacology and Clinical Neuroscience (J.L., L.F.), Umeå University, Sweden.
Jan
J
Linder
From the Clinical Memory Research Unit (O.H., S.J., S.H.), Department of Clinical Sciences, Lund University; Memory Clinic (O.H., S.J., S.H.), Skåne University Hospital, Sweden; UCL Institute of Neurology (N.M., A.J.L., H.Z.), Queen Square, London, UK; Clinical Neurochemistry Laboratory (R.C., H.Z., K.B.), Institute of Neuroscience and Physiology (U.A.), The Sahlgrenska Academy at University of Gothenburg, Mölndal; UmanDiagnostics (N.N.), Umeå; and Department of Pharmacology and Clinical Neuroscience (J.L., L.F.), Umeå University, Sweden.
Lars
L
Forsgren
From the Clinical Memory Research Unit (O.H., S.J., S.H.), Department of Clinical Sciences, Lund University; Memory Clinic (O.H., S.J., S.H.), Skåne University Hospital, Sweden; UCL Institute of Neurology (N.M., A.J.L., H.Z.), Queen Square, London, UK; Clinical Neurochemistry Laboratory (R.C., H.Z., K.B.), Institute of Neuroscience and Physiology (U.A.), The Sahlgrenska Academy at University of Gothenburg, Mölndal; UmanDiagnostics (N.N.), Umeå; and Department of Pharmacology and Clinical Neuroscience (J.L., L.F.), Umeå University, Sweden.
Radu
R
Constantinescu
From the Clinical Memory Research Unit (O.H., S.J., S.H.), Department of Clinical Sciences, Lund University; Memory Clinic (O.H., S.J., S.H.), Skåne University Hospital, Sweden; UCL Institute of Neurology (N.M., A.J.L., H.Z.), Queen Square, London, UK; Clinical Neurochemistry Laboratory (R.C., H.Z., K.B.), Institute of Neuroscience and Physiology (U.A.), The Sahlgrenska Academy at University of Gothenburg, Mölndal; UmanDiagnostics (N.N.), Umeå; and Department of Pharmacology and Clinical Neuroscience (J.L., L.F.), Umeå University, Sweden.
Henrik
H
Zetterberg
From the Clinical Memory Research Unit (O.H., S.J., S.H.), Department of Clinical Sciences, Lund University; Memory Clinic (O.H., S.J., S.H.), Skåne University Hospital, Sweden; UCL Institute of Neurology (N.M., A.J.L., H.Z.), Queen Square, London, UK; Clinical Neurochemistry Laboratory (R.C., H.Z., K.B.), Institute of Neuroscience and Physiology (U.A.), The Sahlgrenska Academy at University of Gothenburg, Mölndal; UmanDiagnostics (N.N.), Umeå; and Department of Pharmacology and Clinical Neuroscience (J.L., L.F.), Umeå University, Sweden.
Kaj
K
Blennow
D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000175:diagnosis; D016900:Neurofilament Proteins / Q000097:blood*; D010300:Parkinson Disease / Q000097:blood* / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D013223:Statistics as Topic; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis
D015415:Biomarkers; D016900:Neurofilament Proteins; C044882:neurofilament protein L