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March 07, 2017; 88 (10) ArticleOpen Access

Blood-based NfL

A biomarker for differential diagnosis of parkinsonian disorder

Oskar Hansson, Shorena Janelidze, Sara Hall, Nadia Magdalinou, Andrew J. Lees, Ulf Andreasson, Niklas Norgren, Jan Linder, Lars Forsgren, Radu Constantinescu, Henrik Zetterberg, Kaj Blennow, For the Swedish BioFINDER study
First published February 8, 2017, DOI: https://doi.org/10.1212/WNL.0000000000003680
Oskar 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.
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Shorena 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.
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Sara 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.
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Nadia 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.
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Andrew J. 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.
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Ulf 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.
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Niklas 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.
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Jan 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.
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Lars 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.
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Radu 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.
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Henrik 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.
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Kaj Blennow
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.
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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.
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Citation
Blood-based NfL
A biomarker for differential diagnosis of parkinsonian disorder
Oskar Hansson, Shorena Janelidze, Sara Hall, Nadia Magdalinou, Andrew J. Lees, Ulf Andreasson, Niklas Norgren, Jan Linder, Lars Forsgren, Radu Constantinescu, Henrik Zetterberg, Kaj Blennow, For the Swedish BioFINDER study
Neurology Mar 2017, 88 (10) 930-937; DOI: 10.1212/WNL.0000000000003680

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    Figure 1 Correlations between blood and CSF levels of neurofilament light chain (NfL)

    Blood and CSF NfL concentrations were measured in the Lund (A) and London (B) cohorts. NfL measurements of matched CSF samples were available for 245 participants in the Lund cohort (147 Parkinson disease [PD], 28 multiple system atrophy [MSA], 15 progressive supranuclear palsy [PSP], 5 corticobasal syndrome [CBS], and 50 controls) and 97 participants in the London cohort (5 PD, 29 MSA, 26 PSP, 11 CBS, and 26 controls).

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    Figure 2 Blood neurofilament light chain (NfL) in different diagnostic groups

    Blood concentrations of NfL in the Lund (A), London (B), and early disease (C) cohorts; p values are from univariate general linear models adjusting for age and sex; *p < 0.05; **p < 0.01; ***p < 0.001. One progressive supranuclear palsy (PSP) case in the early disease cohort with NfL concentration of 134.3 pg/mL is not shown in C (but was included in all statistical analysis). CBS = corticobasal syndrome; MSA = multiple system atrophy; PD = Parkinson disease.

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    Figure 3 Receiver operating characteristic (ROC) curves of blood neurofilament light chain (NfL)

    ROC curves of blood NfL to distinguish Parkinson disease (PD) from atypical parkinsonian disorders (APD) (progressive supranuclear palsy [PSP], multiple system atrophy [MSA], and corticobasal degeneration [CBD]) in the Lund (A), London (B) and early disease (C) cohorts. The early disease cohort included 2 patient groups that were recruited in Göteborg and Umeå, respectively (e-Methods). ROC analysis produced similar results when diagnostic accuracy of blood NfL for differentiating PD from APD was assessed in Göteborg (area under the curve [AUC] 0.80) and Umeå (AUC = 0.81) patients separately.

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