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 Airey, Nicholas K. Proctor, Xiyun Chai, Sergey Shcherbinin, John R. Sims, Gallen Triana‐Baltzer, Clara Theunis, Randy Slemmon, Marc Mercken, Hartmuth C. Kolb, Jeffrey L. Dage, Oskar Hansson
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 [ 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.