ImportancePhosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of p-tau217 tests for research and clinical use has been limited. Expanding access to this highly accurate AD biomarker is crucial for wider evaluation and implementation of AD blood tests.ObjectiveTo determine the utility of a novel and commercially available immunoassay for plasma p-tau217 to detect AD pathology and evaluate reference ranges for abnormal amyloid β (Aβ) and longitudinal change across 3 selected cohorts.Design, Setting, and ParticipantsThis cohort study examined data from 3 single-center observational cohorts: cross-sectional and longitudinal data from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort (visits October 2017–August 2021) and Wisconsin Registry for Alzheimer’s Prevention (WRAP) cohort (visits February 2007–November 2020) and cross-sectional data from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort (baseline visits March 2009–November 2021). Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023.ExposuresMagnetic resonance imaging, Aβ positron emission tomography (PET), tau PET, cerebrospinal fluid (CSF) biomarkers (Aβ42/40 and p-tau immunoassays), and plasma p-tau217 (ALZpath pTau217 assay).Main Outcomes and MeasuresAccuracy of plasma p-tau217 in detecting abnormal amyloid and tau pathology, longitudinal p-tau217 change according to baseline pathology status.ResultsThe study included 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%] and 282 males [35.9%]). High accuracy was observed in identifying elevated Aβ (area under the curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining abnormal PET signal. The detection of abnormal Aβ pathology using a 3-range reference yielded reproducible results and reduced confirmatory testing by approximately 80%. Longitudinally, plasma p-tau217 values showed an annual increase only in Aβ-positive individuals, with the highest increase observed in those with tau positivity.Conclusions and RelevanceThis study found that a commercially available plasma p-tau217 immunoassay accurately identified biological AD, comparable with results using CSF biomarkers, with reproducible cut-offs across cohorts. It detected longitudinal changes, including at the preclinical stage.

中文翻译：

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血浆磷酸化 Tau 217 免疫测定对阿尔茨海默病病理学的诊断准确性

重要性磷酸化 tau (p-tau) 是阿尔茨海默病 (AD) 病理学的一种特异性血液生物标志物，其中 p-tau217 被认为最有用。然而，用于研究和临床用途的 p-tau217 检测的可用性有限。扩大这种高度准确的 AD 生物标志物的使用范围对于更广泛地评估和实施 AD 血液检测至关重要。 目的 确定一种新颖且市售的血浆 p-tau217 免疫测定法在检测 AD 病理学和评估异常淀粉样蛋白 β (Aβ) 的参考范围中的效用）和 3 个选定队列的纵向变化。设计、设置和参与者这项队列研究检查了来自 3 个单中心观察队列的数据：来自衰老和痴呆转化生物标志物 (TRIAD) 队列的横断面和纵向数据（访问 2017 年 10 月– 2021 年 8 月）和威斯康星州阿尔茨海默氏症预防登记处 (WRAP) 队列（2007 年 2 月至 2020 年 11 月访问）以及来自圣保罗神经退行性疾病倡议 (SPIN) 队列的横断面数据（2009 年 3 月至 2021 年 11 月基线访问）。参与者包括有或没有认知障碍的个体，使用 PET 或 CSF 生物标志物按淀粉样蛋白和 tau (AT) 状态进行分组。数据分析时间为 2023 年 2 月至 6 月。暴露磁共振成像、Aβ 正电子发射断层扫描 (PET)、tau PET、脑脊液 (CSF) 生物标志物（Aβ42/40 和 p-tau 免疫测定）和血浆 p-tau217（ALZpath pTau217 测定） ).主要结果和措施血浆 p-tau217 在检测异常淀粉样蛋白和 tau 病理学方面的准确性，根据基线病理状态的纵向 p-tau217 变化。结果该研究包括 786 名参与者（平均 [SD] 年龄，66.3 [9.7] 岁；504 名女性[64.1%] 和 282 名男性 [35.9%]）。所有队列中 Aβ 升高（曲线下面积 [AUC]，0.92-0.96；95% CI，0.89-0.99）和 tau 病理学升高（AUC，0.93-0.97；95% CI，0.84-0.99）均具有较高准确度。在确定异常 PET 信号方面，这些准确性与 CSF 生物标志物相当。使用 3 范围参考检测异常 Aβ 病理学产生了可重复的结果，并将验证性测试减少了约 80%。纵向来看，血浆 p-tau217 值仅在 Aβ 阳性个体中呈逐年增加，其中在 tau 阳性个体中观察到的增加最高。结论和相关性本研究发现，市售血浆 p-tau217 免疫测定法可以准确识别生物 AD，与使用脑脊液生物标志物得出的结果，在队列之间具有可重复的截止值。它检测到纵向变化，包括在临床前阶段。