Plasma P-tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia

Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer’s disease (AD), but its usefulness for differential diagnosis and prognosis is unclear. We studied plasma P-tau181 in three cohorts, with a total of 589 individuals, including cognitively unimpaired participants and patients wit...

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Published in	Nature medicine Vol. 26; no. 3; pp. 379 - 386
Main Authors	Janelidze, Shorena, Mattsson, Niklas, Palmqvist, Sebastian, Smith, Ruben, Beach, Thomas G., Serrano, Geidy E., Chai, Xiyun, Proctor, Nicholas K., Eichenlaub, Udo, Zetterberg, Henrik, Blennow, Kaj, Reiman, Eric M., Stomrud, Erik, Dage, Jeffrey L., Hansson, Oskar
Format	Journal Article
Language	English
Published	New York Nature Publishing Group US 01.03.2020 Nature Publishing Group
Subjects	692/53 692/617 692/617/375/132/1283 Aged Alzheimer Disease - blood Alzheimer Disease - diagnosis Alzheimer Disease - pathology Alzheimer's disease Amyloid beta-Peptides - metabolism amyloid-beta Autopsies Autopsy Biochemistry & Molecular Biology Biological markers Biomarkers Biomarkers - blood Biomedical and Life Sciences Biomedicine Cancer Research Care and treatment Cell and Molecular Biology Cell Biology Cell- och molekylärbiologi Cerebrospinal fluid Clinical Medicine Clinical trials clinical-diagnosis Cognitive ability cross-validation csf t-tau Dementia Dementia - blood Dementia disorders Development and progression Diagnosis Diagnosis, Differential Diagnostic systems Differential diagnosis Disease Disease Progression f-18-av-1451 Female Humans Infectious Diseases Klinisk medicin Longitudinal Studies Male Medical and Health Sciences Medical research Medicin och hälsovetenskap Medicine Medicine, Experimental Metabolic Diseases Middle Aged mild cognitive impairment Molecular Medicine Multivariate Analysis national institute Neurodegenerative diseases Neurologi Neurology Neuropathology Neurosciences p-tau Phosphorylation Positron emission Positron emission tomography Proportional Hazards Models Research & Experimental ROC Curve supranuclear palsy Tau protein tau Proteins - blood Tomography Sweden
Online Access	Get full text
ISSN	1078-8956 1546-170X 1546-170X
DOI	10.1038/s41591-020-0755-1

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Abstract	Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer’s disease (AD), but its usefulness for differential diagnosis and prognosis is unclear. We studied plasma P-tau181 in three cohorts, with a total of 589 individuals, including cognitively unimpaired participants and patients with mild cognitive impairment (MCI), AD dementia and non-AD neurodegenerative diseases. Plasma P-tau181 was increased in preclinical AD and further increased at the MCI and dementia stages. It correlated with CSF P-tau181 and predicted positive Tau positron emission tomography (PET) scans (area under the curve (AUC) = 0.87–0.91 for different brain regions). Plasma P-tau181 differentiated AD dementia from non-AD neurodegenerative diseases with an accuracy similar to that of Tau PET and CSF P-tau181 (AUC = 0.94–0.98), and detected AD neuropathology in an autopsy-confirmed cohort. High plasma P-tau181 was associated with subsequent development of AD dementia in cognitively unimpaired and MCI subjects. In conclusion, plasma P-tau181 is a noninvasive diagnostic and prognostic biomarker of AD, which may be useful in clinical practice and trials. Plasma P-tau18 level increased with progression of Alzheimer’s disease (AD) and differentiated AD dementia from other neurodegenerative diseases, supporting its further development as a blood-based biomarker for AD.
AbstractList	Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer's disease (AD), but its usefulness for differential diagnosis and prognosis is unclear. We studied plasma P-tau181 in three cohorts, with a total of 589 individuals, including cognitively unimpaired participants and patients with mild cognitive impairment (MCI), AD dementia and non-AD neurodegenerative diseases. Plasma P-tau181 was increased in preclinical AD and further increased at the MCI and dementia stages. It correlated with CSF P-tau181 and predicted positive Tau positron emission tomography (PET) scans (area under the curve (AUC) = 0.87-0.91 for different brain regions). Plasma P-tau181 differentiated AD dementia from non-AD neurodegenerative diseases with an accuracy similar to that of Tau PET and CSF P-tau181 (AUC = 0.94-0.98), and detected AD neuropathology in an autopsy-confirmed cohort. High plasma P-tau181 was associated with subsequent development of AD dementia in cognitively unimpaired and MCI subjects. In conclusion, plasma P-tau181 is a noninvasive diagnostic and prognostic biomarker of AD, which may be useful in clinical practice and trials. Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer's disease (AD), but its usefulness for differential diagnosis and prognosis is unclear. We studied plasma P-tau181 in three cohorts, with a total of 589 individuals, including cognitively unimpaired participants and patients with mild cognitive impairment (MCI), AD dementia and non-AD neurodegenerative diseases. Plasma P-tau181 was increased in preclinical AD and further increased at the MCI and dementia stages. It correlated with CSF P-tau181 and predicted positive Tau positron emission tomography (PET) scans (area under the curve (AUC) = 0.87-0.91 for different brain regions). Plasma P-tau181 differentiated AD dementia from non-AD neurodegenerative diseases with an accuracy similar to that of Tau PET and CSF P-tau181 (AUC = 0.94-0.98), and detected AD neuropathology in an autopsy-confirmed cohort. High plasma P-tau181 was associated with subsequent development of AD dementia in cognitively unimpaired and MCI subjects. In conclusion, plasma P-tau181 is a noninvasive diagnostic and prognostic biomarker of AD, which may be useful in clinical practice and trials. Plasma P-tau18 level increased with progression of Alzheimer's disease (AD) and differentiated AD dementia from other neurodegenerative diseases, supporting its further development as a blood-based biomarker for AD. Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer’s disease (AD), but its usefulness for differential diagnosis and prognosis is unclear. We studied plasma P-tau181 in three cohorts, with a total of 589 individuals, including cognitively unimpaired participants and patients with mild cognitive impairment (MCI), AD dementia and non-AD neurodegenerative diseases. Plasma P-tau181 was increased in preclinical AD and further increased at the MCI and dementia stages. It correlated with CSF P-tau181 and predicted positive Tau positron emission tomography (PET) scans (area under the curve (AUC) = 0.87–0.91 for different brain regions). Plasma P-tau181 differentiated AD dementia from non-AD neurodegenerative diseases with an accuracy similar to that of Tau PET and CSF P-tau181 (AUC = 0.94–0.98), and detected AD neuropathology in an autopsy-confirmed cohort. High plasma P-tau181 was associated with subsequent development of AD dementia in cognitively unimpaired and MCI subjects. In conclusion, plasma P-tau181 is a noninvasive diagnostic and prognostic biomarker of AD, which may be useful in clinical practice and trials. Plasma P-tau18 level increased with progression of Alzheimer’s disease (AD) and differentiated AD dementia from other neurodegenerative diseases, supporting its further development as a blood-based biomarker for AD. Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer's disease (AD), but its usefulness for differential diagnosis and prognosis is unclear. We studied plasma P-tau181 in three cohorts, with a total of 589 individuals, including cognitively unimpaired participants and patients with mild cognitive impairment (MCI), AD dementia and non-AD neurodegenerative diseases. Plasma P-tau181 was increased in preclinical AD and further increased at the MCI and dementia stages. It correlated with CSF P-tau181 and predicted positive Tau positron emission tomography (PET) scans (area under the curve (AUC) = 0.87-0.91 for different brain regions). Plasma P-tau181 differentiated AD dementia from non-AD neurodegenerative diseases with an accuracy similar to that of Tau PET and CSF P-tau181 (AUC = 0.94-0.98), and detected AD neuropathology in an autopsy-confirmed cohort. High plasma P-tau181 was associated with subsequent development of AD dementia in cognitively unimpaired and MCI subjects. In conclusion, plasma P-tau181 is a noninvasive diagnostic and prognostic biomarker of AD, which may be useful in clinical practice and trials.Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer's disease (AD), but its usefulness for differential diagnosis and prognosis is unclear. We studied plasma P-tau181 in three cohorts, with a total of 589 individuals, including cognitively unimpaired participants and patients with mild cognitive impairment (MCI), AD dementia and non-AD neurodegenerative diseases. Plasma P-tau181 was increased in preclinical AD and further increased at the MCI and dementia stages. It correlated with CSF P-tau181 and predicted positive Tau positron emission tomography (PET) scans (area under the curve (AUC) = 0.87-0.91 for different brain regions). Plasma P-tau181 differentiated AD dementia from non-AD neurodegenerative diseases with an accuracy similar to that of Tau PET and CSF P-tau181 (AUC = 0.94-0.98), and detected AD neuropathology in an autopsy-confirmed cohort. High plasma P-tau181 was associated with subsequent development of AD dementia in cognitively unimpaired and MCI subjects. In conclusion, plasma P-tau181 is a noninvasive diagnostic and prognostic biomarker of AD, which may be useful in clinical practice and trials.
Audience	Academic
Author	Janelidze, Shorena Eichenlaub, Udo Zetterberg, Henrik Mattsson, Niklas Palmqvist, Sebastian Smith, Ruben Dage, Jeffrey L. Hansson, Oskar Chai, Xiyun Stomrud, Erik Serrano, Geidy E. Reiman, Eric M. Blennow, Kaj Proctor, Nicholas K. Beach, Thomas G.
Author_xml	– sequence: 1 givenname: Shorena orcidid: 0000-0003-2869-8378 surname: Janelidze fullname: Janelidze, Shorena email: shorena.janelidze@med.lu.se organization: Clinical Memory Research Unit, Lund University – sequence: 2 givenname: Niklas surname: Mattsson fullname: Mattsson, Niklas organization: Clinical Memory Research Unit, Lund University, Department of Neurology, Skåne University Hospital, Wallenberg Center for Molecular Medicine, Lund University – sequence: 3 givenname: Sebastian surname: Palmqvist fullname: Palmqvist, Sebastian organization: Clinical Memory Research Unit, Lund University, Department of Neurology, Skåne University Hospital – sequence: 4 givenname: Ruben surname: Smith fullname: Smith, Ruben organization: Clinical Memory Research Unit, Lund University, Department of Neurology, Skåne University Hospital – sequence: 5 givenname: Thomas G. surname: Beach fullname: Beach, Thomas G. organization: Banner Sun Health Research Institute – sequence: 6 givenname: Geidy E. surname: Serrano fullname: Serrano, Geidy E. organization: Banner Sun Health Research Institute – sequence: 7 givenname: Xiyun surname: Chai fullname: Chai, Xiyun organization: Eli Lilly and Company – sequence: 8 givenname: Nicholas K. surname: Proctor fullname: Proctor, Nicholas K. organization: Eli Lilly and Company – sequence: 9 givenname: Udo surname: Eichenlaub fullname: Eichenlaub, Udo organization: Roche Diagnostics GmbH – sequence: 10 givenname: Henrik surname: Zetterberg fullname: Zetterberg, Henrik organization: Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Department of Neurodegenerative Disease, UCL Institute of Neurology, UK Dementia Research Institute at UCL – sequence: 11 givenname: Kaj surname: Blennow fullname: Blennow, Kaj organization: Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital – sequence: 12 givenname: Eric M. orcidid: 0000-0002-0705-3696 surname: Reiman fullname: Reiman, Eric M. organization: Banner Alzheimer’s Institute – sequence: 13 givenname: Erik surname: Stomrud fullname: Stomrud, Erik organization: Clinical Memory Research Unit, Lund University, Memory Clinic, Skåne University Hospital – sequence: 14 givenname: Jeffrey L. surname: Dage fullname: Dage, Jeffrey L. organization: Eli Lilly and Company – sequence: 15 givenname: Oskar orcidid: 0000-0001-8467-7286 surname: Hansson fullname: Hansson, Oskar email: Oskar.Hansson@med.lu.se organization: Clinical Memory Research Unit, Lund University, Memory Clinic, Skåne University Hospital
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/32123385$$D View this record in MEDLINE/PubMed https://gup.ub.gu.se/publication/291206$$DView record from Swedish Publication Index
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Snippet	Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer’s disease (AD), but its usefulness for differential diagnosis and prognosis is unclear.... Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer's disease (AD), but its usefulness for differential diagnosis and prognosis is unclear....
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SubjectTerms	692/53 692/617 692/617/375/132/1283 Aged Alzheimer Disease - blood Alzheimer Disease - diagnosis Alzheimer Disease - pathology Alzheimer's disease Amyloid beta-Peptides - metabolism amyloid-beta Autopsies Autopsy Biochemistry & Molecular Biology Biological markers Biomarkers Biomarkers - blood Biomedical and Life Sciences Biomedicine Cancer Research Care and treatment Cell and Molecular Biology Cell Biology Cell- och molekylärbiologi Cerebrospinal fluid Clinical Medicine Clinical trials clinical-diagnosis Cognitive ability cross-validation csf t-tau Dementia Dementia - blood Dementia disorders Development and progression Diagnosis Diagnosis, Differential Diagnostic systems Differential diagnosis Disease Disease Progression f-18-av-1451 Female Humans Infectious Diseases Klinisk medicin Longitudinal Studies Male Medical and Health Sciences Medical research Medicin och hälsovetenskap Medicine Medicine, Experimental Metabolic Diseases Middle Aged mild cognitive impairment Molecular Medicine Multivariate Analysis national institute Neurodegenerative diseases Neurologi Neurology Neuropathology Neurosciences p-tau Phosphorylation Positron emission Positron emission tomography Proportional Hazards Models Research & Experimental ROC Curve supranuclear palsy Tau protein tau Proteins - blood Tomography
Title	Plasma P-tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia
URI	https://link.springer.com/article/10.1038/s41591-020-0755-1 https://www.ncbi.nlm.nih.gov/pubmed/32123385 https://www.proquest.com/docview/2376202241 https://www.proquest.com/docview/2370492172 https://gup.ub.gu.se/publication/291206
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