Head‐to‐Head evaluation of plasma <i>p</i> ‐tau217 associations with MK6240, Flortaucipir, PI2620, and RO948 tau PET tracers

Abstract Background Tau phosphorylation and aggregation are hallmark features of Alzheimer's disease pathology(AD). Previous studies have shown that plasma phosphorylated tau( p ‐tau) at threonine 217 can detect AD‐related tau tangle pathology. However, the head‐to‐head association between p ‐tau217 and different tau PET tracers remains unexplored. Here, we conducted a head‐to‐head comparison of the association between plasma p ‐tau217 and four distinct tau PET tracers[MK6240, Flortaucipir(FTP), PI2620, RO948]. Method We studied 338 individuals across the AD continuum from the HEAD study[190 cognitively unimpaired elderly(CU), 109 with mild cognitive impairment(MCI), and 39 with dementia] with available FTP, MK6240, and plasma p ‐tau217 measured by ALZpath assay. A subset of 64 individuals(28 CU, 25 MCI, and 11 dementia) also had PI2620 and RO948, and p ‐tau217 measured by Lumipulse. The strength of the association was determined using t‐value maps from regression models testing the association between each tau PET tracer and plasma p ‐tau217, and the extent was measured by the percentage of significant voxels(t‐value&gt;3.2). R‐square metric was used to determine how much of the variance in tau PET tracer estimates was explained by plasma p ‐tau217 concentrations. Associations between p ‐tau217 with tau PET were evaluated using the Spearman test. Result We found that in CU, both the extent and magnitude of the association with plasma p ‐tau217 were higher for MK6240 compared to FTP (Figure 1A‐D). Plasma p ‐tau217 explained a greater proportion of the variance in MK6240 than in FTP (Figure 1E‐F). In CI, the extent and magnitude of the association were similar for MK6240 and FTP. Additionally, plasma p ‐tau217 explained a similar proportion of the variance in MK6240 and FTP. Using the subset of individuals who had all tau tracers, MK6240 showed a slightly higher extent of association with p ‐tau217, followed by FTP, PI2620, and RO948 (Figure 2A‐B). The magnitude of association was stronger for MK6240, followed by PI2620, RO948, and FTP (Figure 2C‐D). Plasma p ‐tau217 explained a greater proportion of the variance in MK6240, followed by FTP, RO948, and PI2620 (Figure 2E‐F). We compared the associations between different p ‐tau217 assays, and both assays presented similar associations with all tau PET tracers (Figure 3). Conclusion In summary, our results indicate that the four tau PET tracers exhibit robust associations with plasma p ‐tau217 in similar topographical regions.