Head-to-head study of diagnostic accuracy of plasma and cerebrospinal fluid p -tau217 versus p -tau181 and p -tau231 in a memory clinic cohort

Background and objective Phosphorylated tau ( p -tau) 217 has recently received attention because it seems more reliable than other p -tau variants for identifying Alzheimer’s disease (AD) pathology. Thus, we aimed to compare the diagnostic accuracy of plasma and CSF p -tau217 with p -tau181 and p -tau231 in a memory clinic cohort. Methods The study included 114 participants (CU = 33; MCI = 67; Dementia = 14). The p -tau variants were correlated versus continuous measures of amyloid (A) and tau (T)-PET. The p -tau phospho-epitopes were assessed through: (i) effect sizes ( δ ) between diagnostic and A ± and T ± groups; (ii) receiver operating characteristic (ROC) analyses in A-PET and T-PET. Results The correlations between both plasma and CSF p -tau217 with A-PET and T-PET ( r range 0.64–0.83) were stronger than those of p -tau181 ( r range 0.44–0.79) and p -tau231 ( r range 0.46–0.76). Plasma p -tau217 showed significantly higher diagnostic accuracy than p -tau181 and p -tau231 in (i) differences between diagnostic and biomarker groups ( δ range : p -tau217 = 0.55–0.96; p -tau181 = 0.51–0.67; p -tau231 = 0.53–0.71); (ii) ROC curves to identify A-PET and T-PET positivity (AUC average : p -tau217 = 0.96; p -tau181 = 0.76; p -tau231 = 0.79). On the other hand, CSF p -tau217 (AUC average = 0.95) did not reveal significant differences in A-PET and T-PET AUC than p -tau181 (AUC average = 0.88) and p -tau231 (AUC average = 0.89). Discussion Plasma p -tau217 demonstrated better performance in the identification of AD pathology and clinical phenotypes in comparison with other variants of p -tau in a memory clinic cohort. Furthermore, p -tau217 had comparable performance in plasma and CSF. Our findings suggest the potential of plasma p -tau217 in the diagnosis and screening for AD, which could allow for a decreased use of invasive biomarkers in the future.