Plasma tau in Alzheimer disease.
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.
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. niklas.mattsson@med.lu.se.
Niklas
N
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.
Henrik
H
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.
Shorena
S
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.
Philip S
PS
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.
Ulf
U
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.
Erik
E
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.
Sebastian
S
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.
David
D
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.
Cristina A
CA
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.
Andreas
A
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.
David
D
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.
Linan
L
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.
Leslie M
LM
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.
John Q
JQ
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.
Michael W
MW
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.
Oskar
O
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.
Kaj
K
Blennow
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid / Q000150:complications; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology; D015331:Cohort Studies; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D016875:tau Proteins / Q000097:blood*
D016229:Amyloid beta-Peptides; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18
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