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

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. Tau can be phosphorylated at multiple other sites including threonine 217, and here we investigated 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 had stronger correlations with the tau PET tracer [ 18 F]flortaucipir, and more accurately identified individuals with abnormally increased [ 18 F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 were higher compared to p-tau181 and better correlated with [ 18 F]flortaucipir retention. P-tau217 correlated better than p-tau181 with PET measures of neocortical amyloid-β burden and more accurately distinguished AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [ 18 F]flortaucipir were corroborated in an independent EXPEDITION3 trial cohort (n=32). These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.