Prospective evaluation of plasma pTau217 stability for the detection of Alzheimer's disease in a tertiary memory clinic.

IF 7.6 1区 医学 Q1 CLINICAL NEUROLOGY
Javier Arranz, Rosa Ferrer, Nuole Zhu, Sara Rubio-Guerra, Íñigo Rodríguez-Baz, José Enrique Arriola-Infante, Lucía Maure-Blesa, Jesús Garcia-Castro, Judit Selma-González, María Carmona-Iragui, Isabel Barroeta, Ignacio Illán-Gala, Miguel Santos-Santos, Juan Fortea, Alberto Lleó, Mireia Tondo, Daniel Alcolea
{"title":"Prospective evaluation of plasma pTau<sub>217</sub> stability for the detection of Alzheimer's disease in a tertiary memory clinic.","authors":"Javier Arranz, Rosa Ferrer, Nuole Zhu, Sara Rubio-Guerra, Íñigo Rodríguez-Baz, José Enrique Arriola-Infante, Lucía Maure-Blesa, Jesús Garcia-Castro, Judit Selma-González, María Carmona-Iragui, Isabel Barroeta, Ignacio Illán-Gala, Miguel Santos-Santos, Juan Fortea, Alberto Lleó, Mireia Tondo, Daniel Alcolea","doi":"10.1186/s13195-025-01779-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Knowledge on the effect of analytical variability and storage conditions are essential for the successful implementation of plasma pTau<sub>217</sub> in prospective settings.</p><p><strong>Aims: </strong>To investigate the performance of plasma pTau<sub>217</sub>, measured in consecutive samples with LUMIPULSE, for detecting Alzheimer's disease in a prospective memory clinic setting, along with evaluating its pre-analytical and analytical stability.</p><p><strong>Methods: </strong>We prospectively measured pTau<sub>217</sub> using the LUMIPULSE automated platform in consecutive patient plasma samples collected between May and November 2024 at the Sant Pau Memory Unit (Barcelona). A subset of participants also underwent paired lumbar puncture for CSF AD biomarkers. We compared biomarker concentrations under different short-term storage conditions (4ºC vs -20ºC) and different protocol pipelines, and assessed lot-to-lot variability. In the subset with available CSF biomarkers, logistic regression was used to evaluate the association between plasma pTau217 and the likelihood of a positive (A +) or a negative (A-) CSF amyloid status. Using ROC analysis, in this prospective cohort we evaluated the accuracy of previously established thresholds derived from historical samples.</p><p><strong>Results: </strong>We included 280 participants, divided into two groups: those with (n = 109) and without CSF data (n = 171). Among the subset with CSF, 48% were A + , with a plasma pTau<sub>217</sub> fold-change of 4.5 × compared to A-. We found no differences in plasma pTau<sub>217</sub> concentrations between either short-term storage conditions. The overall coefficients of analytical variation ranged from 1.8% to 3.2%. Plasma pTau<sub>217</sub> concentrations were slightly higher in paired samples of the clinical protocol. Following a two-threshold approach, the need of confirmatory tests (grey zones) after measuring plasma pTau<sub>217</sub> ranged between 45.9% and 18.3% using our previously reported strict or lenient cutoffs (overall accuracy 96.6% and 92.1%, respectively).</p><p><strong>Conclusions: </strong>The robust stability and low lot-to-lot variability of plasma pTau<sub>217</sub> measurement in an automated platform result in high diagnostic performance of this biomarker in the prospective evaluation of patients in a memory clinic setting. These findings support its implementation into clinical routine, offering clinicians an accessible biomarker for AD diagnosis.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"150"},"PeriodicalIF":7.6000,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228402/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's Research & Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13195-025-01779-7","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Knowledge on the effect of analytical variability and storage conditions are essential for the successful implementation of plasma pTau217 in prospective settings.

Aims: To investigate the performance of plasma pTau217, measured in consecutive samples with LUMIPULSE, for detecting Alzheimer's disease in a prospective memory clinic setting, along with evaluating its pre-analytical and analytical stability.

Methods: We prospectively measured pTau217 using the LUMIPULSE automated platform in consecutive patient plasma samples collected between May and November 2024 at the Sant Pau Memory Unit (Barcelona). A subset of participants also underwent paired lumbar puncture for CSF AD biomarkers. We compared biomarker concentrations under different short-term storage conditions (4ºC vs -20ºC) and different protocol pipelines, and assessed lot-to-lot variability. In the subset with available CSF biomarkers, logistic regression was used to evaluate the association between plasma pTau217 and the likelihood of a positive (A +) or a negative (A-) CSF amyloid status. Using ROC analysis, in this prospective cohort we evaluated the accuracy of previously established thresholds derived from historical samples.

Results: We included 280 participants, divided into two groups: those with (n = 109) and without CSF data (n = 171). Among the subset with CSF, 48% were A + , with a plasma pTau217 fold-change of 4.5 × compared to A-. We found no differences in plasma pTau217 concentrations between either short-term storage conditions. The overall coefficients of analytical variation ranged from 1.8% to 3.2%. Plasma pTau217 concentrations were slightly higher in paired samples of the clinical protocol. Following a two-threshold approach, the need of confirmatory tests (grey zones) after measuring plasma pTau217 ranged between 45.9% and 18.3% using our previously reported strict or lenient cutoffs (overall accuracy 96.6% and 92.1%, respectively).

Conclusions: The robust stability and low lot-to-lot variability of plasma pTau217 measurement in an automated platform result in high diagnostic performance of this biomarker in the prospective evaluation of patients in a memory clinic setting. These findings support its implementation into clinical routine, offering clinicians an accessible biomarker for AD diagnosis.

血浆pta217稳定性对三级记忆临床阿尔茨海默病检测的前瞻性评价
背景:了解分析变异性和储存条件的影响对于在前瞻性环境中成功实施血浆pTau217至关重要。目的:研究血浆pTau217的性能,在LUMIPULSE连续样品中测量,在前瞻性记忆临床环境中检测阿尔茨海默病,同时评估其分析前和分析稳定性。方法:我们使用LUMIPULSE自动化平台对2024年5月至11月在圣保罗记忆中心(Barcelona)收集的连续患者血浆样本进行前瞻性测量。一部分参与者还接受了配对腰椎穿刺检测CSF AD生物标志物。我们比较了不同短期储存条件(4ºC vs -20ºC)和不同方案管道下的生物标志物浓度,并评估了批次间的可变性。在具有可用脑脊液生物标志物的亚组中,使用逻辑回归来评估血浆pTau217与脑脊液淀粉样蛋白阳性(a +)或阴性(a -)状态的可能性之间的关系。使用ROC分析,在这个前瞻性队列中,我们评估了来自历史样本的先前建立的阈值的准确性。结果:我们纳入了280名参与者,分为两组:有脑脊液资料(n = 109)和没有脑脊液资料(n = 171)。在CSF亚群中,48%为A +,血浆pTau217较A-变化4.5倍。我们发现两种短期储存条件下血浆pTau217浓度没有差异。总体分析变异系数为1.8% ~ 3.2%。临床方案配对样本的血浆pTau217浓度略高。采用双阈值方法,在使用我们先前报道的严格或宽松截止值(总体准确度分别为96.6%和92.1%)测量血浆pTau217后,验证性测试(灰色地带)的需求在45.9%至18.3%之间。结论:在一个自动化的平台上,血浆pTau217测量具有强大的稳定性和低批次间变异性,这使得该生物标志物在记忆临床环境中对患者的前瞻性评估中具有很高的诊断性能。这些发现支持将其应用于临床常规,为临床医生提供了一种易于获得的AD诊断生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信