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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
Nature communications, 04/2020, Volume: 11, Issue: 1Journal Article
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 Fflortaucipir, and more accurately identifies individuals with abnormally increased Fflortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with Fflortaucipir 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 Fflortaucipir 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.
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