Discrepancy between plasma pTau181 and tau‐PET statuses

Abstract

AbstractBackgroundAssessments of tau usually come from cerebrospinal fluid or Positron Emission Tomography (PET). However, those methods are expensive and not readily available. Current research is focusing on cost‐effective blood‐based biomarkers, and a novel immunoassay for plasma pTau181 has been created. Even though there are strong associations between plasma pTau181 and PET, no study has yet investigated whether plasma pTau181 can be used to detect early AD‐pathology. Does the status of plasma pTau181 always correlate with tau‐PET status?MethodWe assessed 269 individuals from the TRIAD cohort (164 CU, 60 MCI and 45 AD) that underwent plasma pTau181 assessment, [18F]MK6240 tau‐PET scan, [18F]AZD4694 amyloid‐PET scan to assess their amyloid status, an MRI and a neuropsychological evaluation. We conducted statistical analyses using R, first to calculate the threshold values for positivity in both tau assessing methods and to make comparisons between the groups. For tau‐PET, we used [18F]MK6240 SUVR in the temporal meta‐ROI.ResultUsing Receiver Operating Characteristic (ROC) curves, we established that the cut‐off for positivity for plasma pTau181 was 11.1060 pg/mL, while for tau‐PET, it was 1.1827 SUVR. 182 individuals had concordant statuses for both plasma pTau181 and tau‐PET, while 87 were discrepant. 64 were plasma+/PET‐, with a majority cognitively unimpaired (CU) and 23 were plasma‐/PET+, with values close to the thresholds, and mostly MCI or AD (Figure1). Moreover, concomitant plasma/PET statuses were usually accompanied by a similar Ab status (Figure2). CU Ab+ individuals were found in high proportion in the plasma+/PET‐ group (Figure3).ConclusionMost of the participants had concordant statuses for plasma pTau181 and tau‐PET, which correlate well with memory scores and diagnoses. However, there was a significant portion of discordant individuals, which were predominantly plasma+/PET‐. This corroborates findings from comparisons between CSF pTau181 and tau‐PET, with CSF positivity coming before PET. Plasma pTau181 is also a great tool to assess Ab status, even before the onset of tau‐PET abnormalities. Assessing tau through plasma or PET is thought to suggest different stages of pathological progression.