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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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Abstract

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.

Classification of evidence: This study provides Class III evidence that blood NfL levels discriminate between PD and APD.

GLOSSARY

APD=
atypical parkinsonian disorders;
AUC=
area under the curve;
CBD=
corticobasal degeneration;
CBS=
corticobasal syndrome;
CI=
confidence interval;
MSA=
multiple system atrophy;
NfL=
neurofilament light chain;
p-tau=
phosphorylated tau;
PD=
Parkinson disease;
PSP=
progressive supranuclear palsy;
UPDRS=
Unified Parkinson's Disease Rating Scale;
WML=
white matter lesion

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by the Swedish Research Council.

  • Coinvestigators are listed at Neurology.org.

  • Supplemental data at Neurology.org

  • Editorial, page 922

  • Received April 22, 2016.
  • Accepted in final form November 15, 2016.
  • Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

This is an open access article distributed under the terms of the Creative Commons Attribution Licence 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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