Performance of plasma p-tau217 for the detection of amyloid-β positivity in a memory clinic cohort using an electrochemiluminescence immunoassay.

IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY
Adam H Dyer, Helena Dolphin, Antoinette O'Connor, Laura Morrison, Gavin Sedgwick, Conor Young, Emily Killeen, Conal Gallagher, Aoife McFeely, Eimear Connolly, Naomi Davey, Paul Claffey, Paddy Doyle, Shane Lyons, Christine Gaffney, Ruth Ennis, Cathy McHale, Jasmine Joseph, Graham Knight, Emmet Kelly, Cliona O'Farrelly, Aoife Fallon, Sean O'Dowd, Nollaig M Bourke, Sean P Kennelly
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引用次数: 0

Abstract

Background: Plasma p-tau217 has emerged as the most promising blood-based marker (BBM) for the detection of Alzheimer Disease (AD) pathology, yet few studies have evaluated plasma p-tau217 performance in memory clinic settings. We examined the performance of plasma p-tau217 for the detection of AD using a high-sensitivity immunoassay in individuals undergoing diagnostic lumbar puncture (LP).

Methods: Paired plasma and cerebrospinal fluid (CSF) samples were analysed from the TIMC-BRAiN cohort. Amyloid (Aβ) and Tau (T) pathology were classified based on established cut-offs for CSF Aβ42 and CSF p-tau181 respectively. High-sensitivity electrochemiluminescence (ECL) immunoassays were performed on paired plasma/CSF samples for p-tau217, p-tau181, Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light (NfL) and total tau (t-tau). Biomarker performance was evaluated using Receiver-Operating Curve (ROC) and Area-Under-the-Curve (AUC) analysis.

Results: Of 108 participants (age: 69 ± 6.5 years; 54.6% female) with paired samples obtained at time of LP, 64.8% (n = 70/108) had Aβ pathology detected (35 with Mild Cognitive Impairment and 35 with mild dementia). Plasma p-tau217 was over three-fold higher in Aβ + (12.4 pg/mL; 7.3-19.2 pg/mL) vs. Aβ- participants (3.7 pg/mL; 2.8-4.1 pg/mL; Mann-Whitney U = 230, p < 0.001). Plasma p-tau217 exhibited excellent performance for the detection of Aβ pathology (AUC: 0.91; 95% Confidence Interval [95% CI]: 0.86-0.97)-greater than for T pathology (AUC: 0.83; 95% CI: 0.75-0.90; z = 1.75, p = 0.04). Plasma p-tau217 outperformed plasma p-tau181 for the detection of Aβ pathology (z = 3.24, p < 0.001). Of the other BBMs, only plasma GFAP significantly differed by Aβ status which significantly correlated with plasma p-tau217 in Aβ + (but not in Aβ-) individuals. Application of a two-point threshold at 95% and 97.5% sensitivities & specificities may have enabled avoidance of LP in 58-68% of cases.

Conclusions: Plasma p-tau217 measured using a high-sensitivity ECL immunoassay demonstrated excellent performance for detection of Aβ pathology in a real-world memory clinic cohort. Moving forward, clinical use of plasma p-tau217 to detect AD pathology may substantially reduce need for confirmatory diagnostic testing for AD pathology with diagnostic LP in specialist memory services.

用电化学发光免疫测定法检测记忆门诊队列中血浆 p-tau217 的淀粉样蛋白-β阳性率。
背景:血浆p-tau217已成为检测阿尔茨海默病(AD)病理的最有前途的血液标记物(BBM),但很少有研究评估血浆p-tau217在记忆门诊中的表现。我们使用一种高灵敏度免疫测定方法检测了接受诊断性腰椎穿刺(LP)者血浆 p-tau217 在检测 AD 方面的性能:方法:对TIMC-BRAiN队列中的配对血浆和脑脊液(CSF)样本进行分析。淀粉样蛋白(Aβ)和Tau(T)病理学分别根据CSF Aβ42和CSF p-tau181的既定临界值进行分类。对配对血浆/脑脊液样本进行高灵敏度电化学发光(ECL)免疫测定,检测p-tau217、p-tau181、胶质纤维酸性蛋白(GFAP)、神经丝光(NfL)和总tau(t-tau)。生物标记物的性能采用接收者操作曲线(ROC)和曲线下面积(AUC)分析法进行评估:108名参与者(年龄:69 ± 6.5岁;54.6%为女性)在LP时获得了配对样本,其中64.8%(n = 70/108)的参与者检测到了Aβ病变(35人患有轻度认知障碍,35人患有轻度痴呆)。Aβ +参与者(12.4 pg/mL;7.3-19.2 pg/mL)与Aβ-参与者(3.7 pg/mL;2.8-4.1 pg/mL;Mann-Whitney U = 230,p 结论)相比,血浆p-tau217高出三倍多:使用高灵敏度 ECL 免疫测定法测量的血浆 p-tau217 在检测真实世界记忆诊所队列中的 Aβ 病理学方面表现出色。展望未来,临床使用血浆p-tau217检测AD病理变化可能会大大减少专科记忆服务机构对诊断LP的AD病理变化确诊测试的需求。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Alzheimer's Research & Therapy
Alzheimer's Research & Therapy 医学-神经病学
CiteScore
13.10
自引率
3.30%
发文量
172
审稿时长
>12 weeks
期刊介绍: Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.
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