Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease

• Published in: Nature communications Vol. 11; no. 1; pp. 1683 - 12
• Main Authors: Janelidze, Shorena, Stomrud, Erik, Smith, Ruben, Palmqvist, Sebastian, Mattsson, Niklas, Airey, David C., Proctor, Nicholas K., Chai, Xiyun, Shcherbinin, Sergey, Sims, John R., Triana-Baltzer, Gallen, Theunis, Clara, Slemmon, Randy, Mercken, Marc, Kolb, Hartmuth, Dage, Jeffrey L., Hansson, Oskar
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.04.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 692/53/2421; 692/617/375/132/1283; Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Basic Medicine; Biomarkers; Biomarkers - cerebrospinal fluid; Brain; Brain - diagnostic imaging; Carbolines - administration & dosage; Cerebrospinal fluid; Contrast Media - administration & dosage; Dementia disorders; Diagnosis, Differential; Diagnostic systems; Feasibility Studies; Female; Fluorine isotopes; Humanities and Social Sciences; Humans; Immunoassay; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Metabolism; Middle Aged; multidisciplinary; Neocortex; Neurodegenerative diseases; Neurosciences; Neurovetenskaper; Phosphorylation; Positron emission; Positron emission tomography; Science; Science (multidisciplinary); Sweden; Tau protein; tau Proteins - cerebrospinal fluid; tau Proteins - metabolism; Threonine; Tomography; Sweden
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15436-0

Cerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort ( n  = 194), p-tau217 shows stronger correlations with the tau positron emission tomography (PET) tracer [ 18 F]flortaucipir, and more accurately identifies individuals with abnormally increased [ 18 F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [ 18 F]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [ 18 F]flortaucipir are corroborated in an independent EXPEDITION3 trial cohort ( n  = 32). The main results are validated using a different p-tau217 immunoassay. These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD. Cerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD) reflecting abnormal tau metabolism in the AD brain. Here the authors demonstrate that CSF p-tau217 shows better performance as an AD biomarker than p-tau181.