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

Shorena Janelidze (), Erik Stomrud, Ruben Smith, Sebastian Palmqvist, Niklas Mattsson, David C. Airey, Nicholas K. Proctor, Xiyun Chai, Sergey Shcherbinin, John R. Sims, Gallen Triana-Baltzer, Clara Theunis, Randy Slemmon, Marc Mercken, Hartmuth Kolb (), Jeffrey L. Dage () and Oskar Hansson ()
Additional contact information
Shorena Janelidze: Lund University
Erik Stomrud: Lund University
Ruben Smith: Lund University
Sebastian Palmqvist: Lund University
Niklas Mattsson: Lund University
David C. Airey: Eli Lilly and Company
Nicholas K. Proctor: Eli Lilly and Company
Xiyun Chai: Eli Lilly and Company
Sergey Shcherbinin: Eli Lilly and Company
John R. Sims: Eli Lilly and Company
Gallen Triana-Baltzer: Janssen Research & Development
Clara Theunis: Janssen Pharmaceutical Companies of Johnson & Johnson
Randy Slemmon: Janssen Research & Development
Marc Mercken: Janssen Pharmaceutical Companies of Johnson & Johnson
Hartmuth Kolb: Janssen Research & Development
Jeffrey L. Dage: Eli Lilly and Company
Oskar Hansson: Lund University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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 [18F]flortaucipir, and more accurately identifies individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [18F]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 [18F]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.

Date: 2020
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DOI: 10.1038/s41467-020-15436-0

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