血浆 P-tau217 作为一种基于血液的老年痴呆症生物标记物,显示出卓越的诊断和预后性能

IF 6 2区 医学 Q1 GERIATRICS & GERONTOLOGY
Adam Dyer, Helena Dolphin, Laura Morrison, Antoinette O'Connor, Gavin Sedgwick, Conor Young, Emily Killeen, Conal Gallagher, Aoife McFeely, Eimear Connolly, Naomi Davey, Paddy Doyle, Paul Claffey, Shane Lyons, Christine Gaffney, Ruth Ennis, Cathy McHale, Jasmine Joseph, Graham Knight, Emmet Kelly, Cliona O'Farrelly, Aoife Fallon, Sean O'Dowd, Brian Lawlor, Nollaig Bourke, Sean Kennelly
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Two cohorts were studied: (i) a memory clinic validation cohort of 108 older adults (69 ± 6.5 years; 54.6% female) with early cognitive symptoms and paired plasma/cerebrospinal fluid (CSF) at time of diagnostic Lumbar Puncture (LP) and (ii) a broader replication cohort of 446 individuals ranging from cognitively-unimpaired middle-aged adults to older adults with established AD with 18-month follow-up. Plasma P-tau217 performance was examined against clinically established CSF Aβ+/T+ cut-offs using Area-Under the Curve (AUC) analysis. Plasma cut-offs were optimised vs CSF based on maximal Youden index. Results In the memory clinic cohort, plasma p-tau217 exhibited excellent performance for the detection of Aβ pathology (AUC: 0.91, 0.86-0.97). Plasma p-tau217 was nearly 4-fold higher in Aβ+ (13.89; 7.36-19.0pg/mL) vs Aβ- (3.72; 2.80-4.09pg/mL, U = 230, p<0.001) participants. Plasma p-tau217 was superior in the identification of Aβ vs T pathology (p<0.05, DeLong Test) and outperformed p-tau181 and other BBMs(all p<0.05, DeLong Test). In the replication cohort, plasma p-tau217 maintained >90% accuracy for clinical AD and was significantly associated with clinically meaningful cognitive decline over 18 months (Odds Ratio 1.40; 1.06-1.85, p=0.02). In the initial memory clinic cohort, application of plasma p-tau217 as a diagnostic test would have reduced the need for LPs by over half (56.5%). Conclusion Plasma p-217 demonstrates excellent diagnostic and prognostic performance in older adults with AD, representing an amyloid-responsive measure which also predicts meaningful cognitive decline in established AD. 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引用次数: 0

摘要

背景 基于血液的生物标记物(BBMs)的开发取得了前所未有的进展,如用于检测阿尔茨海默病(AD)病理的 p-tau217,其特征是淀粉样蛋白-β(Aβ)和高磷酸化 tau(T)的积累。然而,BBM在 "真实世界 "记忆门诊中的表现仍不清楚。方法 使用高灵敏度免疫测定法对 554 名参与者的血浆 p-tau217 进行评估。研究了两个队列:(i)记忆诊所验证队列,包括108名有早期认知症状的老年人(69 ± 6.5岁;54.6%为女性),诊断性腰椎穿刺(LP)时血浆/脑脊液(CSF)配对;(ii)更广泛的复制队列,包括446人,其中既有认知能力未受损的中年人,也有随访18个月的已确诊AD的老年人。使用曲线下面积(AUC)分析法对照临床确定的脑脊液Aβ+/T+临界值检验血浆P-tau217的性能。根据最大尤登指数对血浆与脑脊液的临界值进行了优化。结果 在记忆门诊队列中,血浆p-tau217在检测Aβ病理学方面表现优异(AUC:0.91,0.86-0.97)。Aβ+(13.89;7.36-19.0pg/mL)与Aβ-(3.72;2.80-4.09pg/mL,U = 230,p<0.001)参试者的血浆p-tau217高出近4倍。血浆p-tau217在鉴别Aβ与T病理方面更具优势(p<0.05,DeLong检验),并且优于p-tau181和其他BBMs(均p<0.05,DeLong检验)。在复制队列中,血浆p-tau217对临床AD的准确率保持在>90%,并且与18个月内有临床意义的认知能力下降显著相关(Odds Ratio 1.40; 1.06-1.85, p=0.02)。在最初的记忆门诊队列中,应用血浆 p-tau217 作为诊断测试可将 LPs 的需求减少一半以上(56.5%)。结论 血浆p-217对患有AD的老年人具有很好的诊断和预后作用,它是一种淀粉样蛋白反应性指标,还能预测已确诊的AD患者有意义的认知功能下降。将血浆p-tau217纳入记忆门诊可大大减少一半以上的LP诊断需求。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Plasma P-tau217 Demonstrates Excellent Diagnostic and Prognostic Performance as a Blood-Based Biomarker for Alzheimer Disease in Older Adults
Background There has been unprecedented progress in the development of blood-based biomarkers (BBMs such as p-tau217 to detect Alzheimer Disease (AD) pathology – characterised by the accumulation of Amyloid-Beta (Aβ) and hyper-phosphorylated tau (T). However, BBM performance in “real-world” memory clinic contexts remains unclear. Methods Using high-sensitivity immunoassays, plasma p-tau217 was assessed in 554 participants. Two cohorts were studied: (i) a memory clinic validation cohort of 108 older adults (69 ± 6.5 years; 54.6% female) with early cognitive symptoms and paired plasma/cerebrospinal fluid (CSF) at time of diagnostic Lumbar Puncture (LP) and (ii) a broader replication cohort of 446 individuals ranging from cognitively-unimpaired middle-aged adults to older adults with established AD with 18-month follow-up. Plasma P-tau217 performance was examined against clinically established CSF Aβ+/T+ cut-offs using Area-Under the Curve (AUC) analysis. Plasma cut-offs were optimised vs CSF based on maximal Youden index. Results In the memory clinic cohort, plasma p-tau217 exhibited excellent performance for the detection of Aβ pathology (AUC: 0.91, 0.86-0.97). Plasma p-tau217 was nearly 4-fold higher in Aβ+ (13.89; 7.36-19.0pg/mL) vs Aβ- (3.72; 2.80-4.09pg/mL, U = 230, p<0.001) participants. Plasma p-tau217 was superior in the identification of Aβ vs T pathology (p<0.05, DeLong Test) and outperformed p-tau181 and other BBMs(all p<0.05, DeLong Test). In the replication cohort, plasma p-tau217 maintained >90% accuracy for clinical AD and was significantly associated with clinically meaningful cognitive decline over 18 months (Odds Ratio 1.40; 1.06-1.85, p=0.02). In the initial memory clinic cohort, application of plasma p-tau217 as a diagnostic test would have reduced the need for LPs by over half (56.5%). Conclusion Plasma p-217 demonstrates excellent diagnostic and prognostic performance in older adults with AD, representing an amyloid-responsive measure which also predicts meaningful cognitive decline in established AD. Incorporation of plasma p-tau217 in memory clinic settings may substantially reduce the need for over half of diagnostic LPs.
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来源期刊
Age and ageing
Age and ageing 医学-老年医学
CiteScore
9.20
自引率
6.00%
发文量
796
审稿时长
4-8 weeks
期刊介绍: Age and Ageing is an international journal publishing refereed original articles and commissioned reviews on geriatric medicine and gerontology. Its range includes research on ageing and clinical, epidemiological, and psychological aspects of later life.
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