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October 25, 2016; 87 (17) ArticleOpen Access

Plasma tau in Alzheimer disease

Niklas Mattsson, Henrik Zetterberg, Shorena Janelidze, Philip S. Insel, Ulf Andreasson, Erik Stomrud, Sebastian Palmqvist, David Baker, Cristina A. Tan Hehir, Andreas Jeromin, David Hanlon, Linan Song, Leslie M. Shaw, John Q. Trojanowski, Michael W. Weiner, Oskar Hansson, Kaj Blennow
First published September 30, 2016, DOI: https://doi.org/10.1212/WNL.0000000000003246
Niklas Mattsson
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Henrik Zetterberg
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Shorena Janelidze
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Philip S. Insel
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Ulf Andreasson
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Erik Stomrud
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Sebastian Palmqvist
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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David Baker
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Cristina A. Tan Hehir
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Andreas Jeromin
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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David Hanlon
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Linan Song
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Leslie M. Shaw
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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John Q. Trojanowski
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Michael W. Weiner
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Oskar Hansson
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Kaj Blennow
From the Clinical Memory Research Unit (N.M., S.J., P.S.I., E.S., S.P., O.H.), Department of Clinical Sciences, Malmö, Lund University; Department of Neurology (N.M., E.S., O.H., S.P.), Skåne University Hospital, Lund; Clinical Neurochemistry Laboratory (H.Z., U.A., K.B.), Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Canpus, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Janssen R&D (D.B.), Titusville, NJ; Diagnostics and Life Sciences (C.A.T.H.), GE Global Research, Niskayuna, NY; Quanterix Corporation (A.J., D.H., L.S.), Lexington, MA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center; and Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco.
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Full PDF
Citation
Plasma tau in Alzheimer disease
Niklas Mattsson, Henrik Zetterberg, Shorena Janelidze, Philip S. Insel, Ulf Andreasson, Erik Stomrud, Sebastian Palmqvist, David Baker, Cristina A. Tan Hehir, Andreas Jeromin, David Hanlon, Linan Song, Leslie M. Shaw, John Q. Trojanowski, Michael W. Weiner, Oskar Hansson, Kaj Blennow
Neurology Oct 2016, 87 (17) 1827-1835; DOI: 10.1212/WNL.0000000000003246

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Abstract

Objective: To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism.

Methods: This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, 18fluorodeoxyglucose-PET, and cognition.

Results: Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ42, but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up.

Conclusions: Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD.

GLOSSARY

Aβ=
β-amyloid;
AD=
Alzheimer disease;
ADAS=
Alzheimer's Disease Assessment Scale–Cognitive subscale;
ADNI=
Alzheimer's Disease Neuroimaging Initiative;
BioFINDER=
Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably;
CI=
confidence interval;
CN=
cognitively healthy control;
DSM-III-R=
Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, Revised;
EPIC=
European Prospective Investigation Into Cancer and Nutrition;
FDG=
18fluorodeoxyglucose;
MCI=
mild cognitive impairment;
MMSE=
Mini-Mental State Examination;
P-tau=
phosphorylated tau;
T-tau=
total tau

Footnotes

  • Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators is available at Neurology.org.

  • 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 authors.

  • Supplemental data at Neurology.org

  • Received October 16, 2015.
  • Accepted in final form July 12, 2016.
  • © 2016 American Academy of Neurology

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

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    • Abstract
    • GLOSSARY
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Neurology | Print ISSN:0028-3878
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