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July 19, 2022; 99 (3) Research ArticleOpen Access

Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light

View ORCID ProfileSuzanne E. Schindler, View ORCID ProfileThomas K. Karikari, View ORCID ProfileNicholas J. Ashton, View ORCID ProfileRachel L. Henson, View ORCID ProfileKevin E. Yarasheski, View ORCID ProfileTim West, Mathew R. Meyer, View ORCID ProfileKristopher M. Kirmess, Yan Li, Benjamin Saef, Krista L. Moulder, David Bradford, View ORCID ProfileAnne M. Fagan, View ORCID ProfileBrian A. Gordon, View ORCID ProfileTammie L.S. Benzinger, View ORCID ProfileJoyce Balls-Berry, View ORCID ProfileRandall J. Bateman, Chengjie Xiong, View ORCID ProfileHenrik Zetterberg, View ORCID ProfileKaj Blennow, View ORCID ProfileJohn C. Morris
First published April 21, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200358
Suzanne E. Schindler
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Thomas K. Karikari
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Nicholas J. Ashton
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Rachel L. Henson
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Kevin E. Yarasheski
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Tim West
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Mathew R. Meyer
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Kristopher M. Kirmess
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Yan Li
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Benjamin Saef
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Krista L. Moulder
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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David Bradford
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Anne M. Fagan
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Brian A. Gordon
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Tammie L.S. Benzinger
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Joyce Balls-Berry
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Randall J. Bateman
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Chengjie Xiong
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Henrik Zetterberg
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Kaj Blennow
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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John C. Morris
From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.
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Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light
Suzanne E. Schindler, Thomas K. Karikari, Nicholas J. Ashton, Rachel L. Henson, Kevin E. Yarasheski, Tim West, Mathew R. Meyer, Kristopher M. Kirmess, Yan Li, Benjamin Saef, Krista L. Moulder, David Bradford, Anne M. Fagan, Brian A. Gordon, Tammie L.S. Benzinger, Joyce Balls-Berry, Randall J. Bateman, Chengjie Xiong, Henrik Zetterberg, Kaj Blennow, John C. Morris
Neurology Jul 2022, 99 (3) e245-e257; DOI: 10.1212/WNL.0000000000200358

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Abstract

Background and Objectives To evaluate whether plasma biomarkers of amyloid (Aβ42/Aβ40), tau (p-tau181 and p-tau231), and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups.

Methods Individuals enrolled in studies of memory and aging who self-identified as African American (AA) were matched 1:1 to self-identified non-Hispanic White (NHW) individuals by age, APOE ε4 carrier status, and cognitive status. Each participant underwent blood and CSF collection, and amyloid PET was performed in 103 participants (68%). Plasma Aβ42/Aβ40 was measured by a high-performance immunoprecipitation–mass spectrometry assay. Plasma p-tau181, p-tau231, and NfL were measured by Simoa immunoassays. CSF Aβ42/Aβ40 and amyloid PET status were used as primary and secondary reference standards of brain amyloidosis, respectively.

Results There were 76 matched pairs of AA and NHW participants (n = 152 total). For both AA and NHW groups, the median age was 68.4 years, 42% were APOE ε4 carriers, and 91% were cognitively normal. AA were less likely than NHW participants to have brain amyloidosis by CSF Aβ42/Aβ40 (22% vs 43% positive; p = 0.003). The receiver operating characteristic area under the curve of CSF Aβ42/Aβ40 status with the plasma biomarkers was as follows: Aβ42/Aβ40, 0.86 (95% CI 0.79–0.92); p-tau181, 0.76 (0.68–0.84); p-tau231, 0.69 (0.60–0.78); and NfL, 0.64 (0.55–0.73). In models predicting CSF Aβ42/Aβ40 status with plasma Aβ42/Aβ40 that included covariates (age, sex, APOE ε4 carrier status, race, and cognitive status), race did not affect the probability of CSF Aβ42/Aβ40 positivity. In similar models based on plasma p-tau181, p-tau231, or NfL, AA participants had a lower probability of CSF Aβ42/Aβ40 positivity (odds ratio 0.31 [95% CI 0.13–0.73], 0.30 [0.13–0.71], and 0.27 [0.12–0.64], respectively). Models of amyloid PET status yielded similar findings.

Discussion Models predicting brain amyloidosis using a high-performance plasma Aβ42/Aβ40 assay may provide an accurate and consistent measure of brain amyloidosis across AA and NHW groups, but models based on plasma p-tau181, p-tau231, and NfL may perform inconsistently and could result in disproportionate misdiagnosis of AA individuals.

Glossary

AA=
African American;
Aβ=
β-amyloid;
AD=
Alzheimer disease;
ADRC=
Alzheimer Disease Research Center;
AUC=
area under the curve;
CDR=
Clinical Dementia Rating;
IQR=
interquartile range;
LP=
lumbar puncture;
NfL=
neurofilament light chain;
NHW=
non-Hispanic White;
OR=
odds ratio;
p-tau181=
tau phosphorylated at position 181;
PiB=
Pittsburgh compound B;
ROC=
receiver operating characteristic;
SUVR=
standardized uptake value ratio;
t-tau=
total tau;
UDS=
Uniform Data Set

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.

  • The Article Processing Charge was funded by NIH.

  • Submitted and externally peer reviewed. The handling editor was Linda Hershey, MD, PhD.

  • Received September 24, 2021.
  • Accepted in final form February 22, 2022.
  • Copyright © 2022 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-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 without permission from the journal.

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