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February 02, 2021; 96 (5) Article

Plasma Tau and Neurofilament Light in Frontotemporal Lobar Degeneration and Alzheimer Disease

View ORCID ProfileIgnacio Illán-Gala, Alberto Lleo, Anna Karydas, Adam M. Staffaroni, Henrik Zetterberg, Rajeev Sivasankaran, Lea T. Grinberg, Salvatore Spina, Joel H. Kramer, Eliana M. Ramos, View ORCID ProfileGiovanni Coppola, View ORCID ProfileRenaud La Joie, Gil D. Rabinovici, David C. Perry, Maria Luisa Gorno-Tempini, William W. Seeley, Bruce L. Miller, Howard J. Rosen, Kaj Blennow, Adam L. Boxer, Julio C. Rojas
First published November 16, 2020, DOI: https://doi.org/10.1212/WNL.0000000000011226
Ignacio Illán-Gala
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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  • ORCID record for Ignacio Illán-Gala
Alberto Lleo
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Anna Karydas
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Adam M. Staffaroni
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Henrik Zetterberg
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Rajeev Sivasankaran
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Lea T. Grinberg
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Salvatore Spina
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Joel H. Kramer
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Eliana M. Ramos
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Giovanni Coppola
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Renaud La Joie
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Gil D. Rabinovici
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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David C. Perry
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Maria Luisa Gorno-Tempini
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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William W. Seeley
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Bruce L. Miller
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Howard J. Rosen
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Kaj Blennow
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Adam L. Boxer
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Julio C. Rojas
From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
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Plasma Tau and Neurofilament Light in Frontotemporal Lobar Degeneration and Alzheimer Disease
Ignacio Illán-Gala, Alberto Lleo, Anna Karydas, Adam M. Staffaroni, Henrik Zetterberg, Rajeev Sivasankaran, Lea T. Grinberg, Salvatore Spina, Joel H. Kramer, Eliana M. Ramos, Giovanni Coppola, Renaud La Joie, Gil D. Rabinovici, David C. Perry, Maria Luisa Gorno-Tempini, William W. Seeley, Bruce L. Miller, Howard J. Rosen, Kaj Blennow, Adam L. Boxer, Julio C. Rojas
Neurology Feb 2021, 96 (5) e671-e683; DOI: 10.1212/WNL.0000000000011226

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Abstract

Objective To test the hypothesis that plasma total tau (t-tau) and neurofilament light chain (NfL) concentrations may have a differential role in the study of frontotemporal lobar degeneration syndromes (FTLD-S) and clinically diagnosed Alzheimer disease syndromes (AD-S), we determined their diagnostic and prognostic value in FTLD-S and AD-S and their sensitivity to pathologic diagnoses.

Methods We measured plasma t-tau and NfL with the Simoa platform in 265 participants: 167 FTLD-S, 43 AD-S, and 55 healthy controls (HC), including 82 pathology-proven cases (50 FTLD-tau, 18 FTLD-TDP, 2 FTLD-FUS, and 12 AD) and 98 participants with amyloid PET. We compared cross-sectional and longitudinal biomarker concentrations between groups, their correlation with clinical measures of disease severity, progression, and survival, and cortical thickness.

Results Plasma NfL, but not plasma t-tau, discriminated FTLD-S from HC and AD-S from HC. Both plasma NfL and t-tau were poor discriminators between FLTD-S and AD-S. In pathology-confirmed cases, plasma NfL was higher in FTLD than AD and in FTLD-TDP compared to FTLD-tau, after accounting for age and disease severity. Plasma NfL, but not plasma t-tau, predicted clinical decline and survival and correlated with regional cortical thickness in both FTLD-S and AD-S. The combination of plasma NfL with plasma t-tau did not outperform plasma NfL alone.

Conclusion Plasma NfL is superior to plasma t-tau for the diagnosis and prediction of clinical progression of FTLD-S and AD-S.

Classification of Evidence This study provides Class III evidence that plasma NfL has superior diagnostic and prognostic performance vs plasma t-tau in FTLD and AD.

Glossary

AD=
Alzheimer disease;
AD-S=
Alzheimer disease syndromes;
ALS-FTD=
amyotrophic lateral sclerosis with frontotemporal dementia;
AUC=
area under the receiver operator characteristic curve;
bvFTD=
behavioral variant frontotemporal dementia;
CBS=
corticobasal syndrome;
CDR+NACC/FTLD-SB=
Clinical Dementia Rating plus National Alzheimer's Coordinating Center FTLD sum of boxes;
FTLD=
frontotemporal lobar degeneration;
FTLD-S=
frontotemporal lobar degeneration syndromes;
HC=
healthy control;
MMSE=
Mini-Mental State Examination;
NfL=
neurofilament light;
nfvPPA=
nonfluent/agrammatic variant of primary progressive aphasia;
PSP=
progressive supranuclear palsy;
t-tau=
total tau;
svPPA=
semantic variant of primary progressive aphasia;
UCSF=
University of California, San Francisco

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Class of Evidence: NPub.org/coe

  • Received March 5, 2020.
  • Accepted in final form September 30, 2020.
  • © 2020 American Academy of Neurology
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Topics Discussed

  • Alzheimer's disease
  • Prognosis
  • Frontotemporal dementia
  • Progressive supranuclear palsy
  • Corticobasal degeneration

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