Streamlining Alzheimer's disease diagnosis: real-world validation of two-cut-off diagnostic models based on plasma p-tau/Aβ42 ratios.

IF 4.6 2区医学 Q1 CLINICAL NEUROLOGY

Journal of Neurology Pub Date : 2026-05-08 DOI:10.1007/s00415-026-13833-x

Martina Poli, Chiara Giuseppina Bonomi, Martina Gaia Di Donna, Ilaria Barberis, Emanuele Luca Ginevra, Marzia Nuccetelli, Sergio Bernardini, Diego Centonze, Alessandro Martorana, Caterina Motta

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引用次数: 0

Abstract

Introduction: Anti-amyloid monoclonal antibodies have increased the need for scalable, minimally invasive biomarkers for Alzheimer's disease (AD). In this single-center cohort study, we evaluated plasma biomarkers performance in detecting biologically defined AD, assessing diagnostic accuracy and generalizability outside dedicated laboratory settings and exploring suitability for clinical implementation.

Methods: We enrolled 204 outpatients referred to the memory clinic of Policlinico "Rome Tor Vergata" who underwent standard work-up, lumbar puncture for cerebrospinal fluid (CSF) biomarkers and paired blood sampling. Among plasma biomarkers, phosphorylated tau (p-tau) 181, p-tau217, and their ratios adjusted for Aβ42 were measured on the Lumipulse platform. AD pathology was defined by CSF p-tau181/Aβ42 ≥ 0.069. ROC analyses estimated AUCs, and a two-cut-off approach targeting 90% sensitivity and specificity classified individuals as low, intermediate, or high AD risk. Subgroup analyses examined the impact of sex, age (< 75, ≥ 75 years), chronic kidney disease, and cognitive impairment (MMSE ≥ 26/30, < 26/30) on plasma biomarker levels.

Results: Among single analytes, plasma p-tau217 showed the highest discriminative capacity (AUC 0.883). Combined ratios improved overall performance (p-tau181/Aβ42, AUC 0.928; p-tau217/Aβ42, AUC 0.894) and reduced intermediate-risk classifications to < 15%, with slightly better performance in women, patients < 75 and cognitively unimpaired. The two-cut-off model improved accuracy and rule-in ability.

Discussion: Plasma p-tau/Aβ42 ratios show high and robust accuracy for detecting CSF-defined AD pathology. A two-step approach based on p-tau181/Aβ42 or p-tau217/Aβ42 could streamline diagnostic workflows in memory clinics, reserving second-line assessments to indeterminate cases and supporting selection of candidates for disease-modifying anti-amyloid therapies.

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简化阿尔茨海默病诊断：基于血浆p-tau/ a - β42比率的双截止诊断模型的现实验证

抗淀粉样蛋白单克隆抗体增加了对阿尔茨海默病（AD）可扩展、微创生物标志物的需求。在这项单中心队列研究中，我们评估了血浆生物标志物在检测生物学定义的AD方面的表现，评估了诊断的准确性和专用实验室环境之外的普遍性，并探索了临床实施的适用性。方法：我们招募了204名到polilinico“Rome Tor Vergata”记忆诊所就诊的门诊患者，他们接受了标准的体检、腰椎穿刺检测脑脊液（CSF）生物标志物和配对血液采样。在血浆生物标志物中，磷酸化tau (p-tau) 181、p-tau217及其Aβ42调整后的比值在Lumipulse平台上进行了测量。脑脊液p-tau181/ a - β42≥0.069定义AD病理。ROC分析估计auc，针对90%敏感性和特异性的双截止方法将个体分为低、中、高风险AD。亚组分析考察了性别、年龄的影响(结果：在单个分析物中，血浆p-tau217表现出最高的判别能力（AUC 0.883）。联合比值提高了总体表现（p-tau181/ a - β42, AUC 0.928; p-tau217/ a - β42, AUC 0.894），并降低了中等风险等级。讨论：血浆p-tau/ a - β42比值在检测csf定义的AD病理方面显示出高而稳健的准确性。基于p-tau181/A - β42或p-tau217/A - β42的两步方法可以简化记忆诊所的诊断工作流程，保留二线评估以确定病例，并支持选择改善疾病的抗淀粉样蛋白疗法的候选药物。

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

Journal of Neurology 医学-临床神经学

CiteScore

10.00

自引率

5.00%

发文量

558

审稿时长

1 months

期刊介绍： The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field. In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials. Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.