Plasma pTau‐217 and N‐terminal tau (NTA) enhance sensitivity to identify tau PET positivity in amyloid‐β positive individuals

Abstract

INTRODUCTIONWe set out to identify tau PET‐positive (A+T+) individuals among amyloid‐beta (Aβ) positive participants using plasma biomarkers.METHODSIn this cross‐sectional study we assessed 234 participants across the AD continuum who were evaluated by amyloid PET with [18F]AZD4694 and tau‐PET with [18F]MK6240 and measured plasma levels of total tau, pTau‐181, pTau‐217, pTau‐231, and N‐terminal tau (NTA‐tau). We evaluated the performances of plasma biomarkers to predict tau positivity in Aβ+ individuals.RESULTSHighest associations with tau positivity in Aβ+ individuals were found for plasma pTau‐217 (AUC [CI95%] = 0.89 [0.82, 0.96]) and NTA‐tau (AUC [CI95%] = 0.88 [0.91, 0.95]). Combining pTau‐217 and NTA‐tau resulted in the strongest agreement (Cohen's Kappa = 0.74, CI95% = 0.57/0.90, sensitivity = 92%, specificity = 81%) with PET for classifying tau positivity.DISCUSSIONThe potential for identifying tau accumulation in later Braak stages will be useful for patient stratification and prognostication in treatment trials and in clinical practice.Highlights We found that in a cohort without pre‐selection pTau‐181, pTau‐217, and NTA‐tau showed the highest association with tau PET positivity. We found that in Aβ+ individuals pTau‐217 and NTA‐tau showed the highest association with tau PET positivity. Combining pTau‐217 and NTA‐tau resulted in the strongest agreement with the tau PET‐based classification.

Aggregation of gold nanoclusters in amyloid fibers: a luminescence assay for amyloid fibrillation detection and inhibitor screening

“…The related studies indicate that the detection of amyloid fibrils commonly occurs in cerebrospinal fluid or human plasma. [42][43][44][45] It appears that the detection of lysozyme fibrosis can exclude interferences from metal ions, amylase, bovine serum albumin (BSA), human serum albumin, alkaline phosphatase, trypsin, DNA and RNA, as described in the literature. 28,46 On the basis of the response of the Au NCs to the fibers, we applied Au NCs to the detection of lysozyme amyloid fibrillation.…”