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

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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.

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Journal

Journal ID (iso-abbrev): Nat Med

Title: Nature medicine

Publisher: Springer Science and Business Media LLC

ISSN (Electronic): 1546-170X

ISSN (Print): 1078-8956

Publication date (Electronic): March 2020

Volume: 26

Issue: 3

Affiliations

[1 ] Clinical Memory Research Unit, Lund University, Lund, Sweden. shorena.janelidze@med.lu.se.

[2 ] Clinical Memory Research Unit, Lund University, Lund, Sweden.

[3 ] Department of Neurology, Skåne University Hospital, Lund, Sweden.

[4 ] Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.

[5 ] Banner Sun Health Research Institute, Sun City, AZ, USA.

[6 ] Eli Lilly and Company, Indianapolis, IN, USA.

[7 ] Roche Diagnostics GmbH, Penzberg, Germany.

[8 ] Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

[9 ] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

[10 ] Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.

[11 ] UK Dementia Research Institute at UCL, London, UK.

[12 ] Banner Alzheimer's Institute, Phoenix, AZ, USA.

[13 ] Memory Clinic, Skåne University Hospital, Malmö, Sweden.

[14 ] Clinical Memory Research Unit, Lund University, Lund, Sweden. Oskar.Hansson@med.lu.se.

[15 ] Memory Clinic, Skåne University Hospital, Malmö, Sweden. Oskar.Hansson@med.lu.se.

Article

Publisher Item ID: 10.1038/s41591-020-0755-1

DOI: 10.1038/s41591-020-0755-1

PubMed ID: 32123385

SO-VID: e4d63295-c2e5-4074-beea-95abd0922235

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

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