Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, Canada.
Alzheimers Dement. 2024 Feb;20(2):1166-1174. doi: 10.1002/alz.13528. Epub 2023 Nov 3.
We set out to identify tau PET-positive (A+T+) individuals among amyloid-beta (Aβ) positive participants using plasma biomarkers.
In this cross-sectional study we assessed 234 participants across the AD continuum who were evaluated by amyloid PET with [ F]AZD4694 and tau-PET with [ F]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.
Highest associations with tau positivity in Aβ+ individuals were found for plasma pTau-217 (AUC [CI ] = 0.89 [0.82, 0.96]) and NTA-tau (AUC [CI ] = 0.88 [0.91, 0.95]). Combining pTau-217 and NTA-tau resulted in the strongest agreement (Cohen's Kappa = 0.74, CI = 0.57/0.90, sensitivity = 92%, specificity = 81%) with PET for classifying tau positivity.
The potential for identifying tau accumulation in later Braak stages will be useful for patient stratification and prognostication in treatment trials and in clinical practice.
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.
我们旨在使用血浆生物标志物在淀粉样蛋白-β（Aβ）阳性参与者中确定 tau PET 阳性（A+T+）个体。
在这项横断面研究中，我们评估了 234 名处于 AD 连续体中的参与者，他们接受了[F]AZD4694 淀粉样蛋白 PET 和[F]MK6240 tau-PET 评估，并测量了总 tau、pTau-181、pTau-217、pTau-231 和 N 端 tau（NTA-tau）的血浆水平。我们评估了血浆生物标志物预测 Aβ+个体中 tau 阳性的性能。
在 Aβ+个体中，与 tau 阳性相关性最高的是血浆 pTau-217（AUC [CI] = 0.89 [0.82, 0.96]）和 NTA-tau（AUC [CI] = 0.88 [0.91, 0.95]）。结合 pTau-217 和 NTA-tau 可使 PET 对 tau 阳性的分类具有最强的一致性（Cohen's Kappa = 0.74，CI = 0.57/0.90，敏感性 = 92%，特异性 = 81%）。
在没有预先选择的情况下识别 tau 积累的后期 Braak 阶段的潜力将有助于在治疗试验和临床实践中对患者进行分层和预后预测。
我们发现，在没有预先选择的情况下，pTau-181、pTau-217 和 NTA-tau 与 tau PET 阳性的相关性最高。我们发现，在 Aβ+个体中，pTau-217 和 NTA-tau 与 tau PET 阳性的相关性最高。结合 pTau-217 和 NTA-tau 与基于 tau PET 的分类具有最强的一致性。
