Journal Article

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

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.

2020

Overview

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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 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