使用Lumipulse自动化平台检测记忆门诊队列中血浆p-tau217的诊断性能。

Diagnostic performance of plasma p-tau217 in a memory clinic cohort using the Lumipulse automated platform.

作者信息

Martínez-Dubarbie Francisco, Guerra-Ruiz Armando, López-García Sara, Lage Carmen, Fernández-Matarrubia Marta, Nevado-Cáceres Álvaro, Rivera-Sánchez María, Valera-Barrero Andrea, Pozueta-Cantudo Ana, García-Martínez María, Corrales-Pardo Andrea, Bravo María, López-Hoyos Marcos, Irure-Ventura Juan, de Lucas Enrique Marco, Drake-Pérez Marta, Cahuana-Santamaría Nancy Heidy, García-Unzueta María Teresa, Sánchez-Juan Pascual, Rodríguez-Rodríguez Eloy

机构信息

Neurology Service, Marqués de Valdecilla University Hospital, Avda. de Valdecilla 25, Santander, Cantabria, 39008, Spain.

Institute for Research Marqués de Valdecilla (IDIVAL), Santander, Cantabria, 39011, Spain.

出版信息

Alzheimers Res Ther. 2025 Mar 27;17(1):68. doi: 10.1186/s13195-025-01719-5.

DOI:10.1186/s13195-025-01719-5

PMID:40140924

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11948696/

Abstract

BACKGROUND

Plasma biomarkers for Alzheimer's disease (AD) are a promising tool for accessible and accurate biological diagnostics. However, data in clinical practice are needed to better understand their diagnostic and prognostic ability in memory unit patients.

METHODS

We analyzed plasma phosphorylated tau at threonine 217 (p-tau217) and neuroflament light chain (NfL) levels and AD cerebrospinal fluid (CSF) biomarkers in a group of 493 subjects using the Lumipulse G600II platform. The sample includes 340 patients from our memory unit (142 dementia, 186 mild cognitive impairment, and 12 with subjective complaints) and 153 cognitively unimpaired volunteers. We have correlated plasma and CSF biomarkers; we have analyzed plasma biomarker levels as a function of clinical diagnosis, cognitive status and amyloid status. We have also studied the ability of p-tau217 to discriminate between amyloid-positive and -negative subjects according to CSF using receiver operating characteristic curves.

RESULTS

Plasma p-tau217 correlated significantly with CSF Aβ42/Aβ40 (Rho = -0.75; p-value < 0.001), p-tau181 (r = 0.66; p-value < 0.001), and t-tau (r = 0.59; p-value < 0.001). Plasma NfL correlated with CSF NfL (r = 0.48; p-value < 0.001). By clinical diagnosis, plasma p-tau217 levels showed to be higher in AD patients than in healthy controls (difference = 0.63 pg/ml; p-value < 0.001), FTD (difference = 0.60 pg/ml; p-value < 0.001), and nondegenerative dementias (difference = 0.61 pg/ml; p-value < 0.001). Plasma p-tau217 showed an area under the curve of 0.95 to discriminate between A + and A- subjects (95%CI 0.93-0.97).

CONCLUSION

Plasma p-tau217 shows excellent results for detecting amyloid pathology at brain level in a clinical setting with an AUC of 0.95. It is a highly specific marker of AD and increases progressively along the disease continuum. Using plasma p-tau217 as an initial diagnostic tool with cut-offs at sensitivities and specificities of 95 or 97.5% could save between 57.4-84.8% of LP/PETs with diagnostic accuracies of 95-97%. Plasma NfL increases progressively at different cognitive stages.

摘要

背景

阿尔茨海默病（AD）的血浆生物标志物是用于便捷且准确的生物学诊断的一种有前景的工具。然而，需要临床实践中的数据来更好地了解它们在记忆科患者中的诊断和预后能力。

方法

我们使用Lumipulse G600II平台分析了493名受试者的血浆苏氨酸217磷酸化tau（p-tau217）和神经丝轻链（NfL）水平以及AD脑脊液（CSF）生物标志物。样本包括来自我们记忆科的340名患者（142例痴呆、186例轻度认知障碍和12例有主观症状者）以及153名认知未受损的志愿者。我们对血浆和脑脊液生物标志物进行了相关性分析；我们分析了血浆生物标志物水平与临床诊断、认知状态和淀粉样蛋白状态的关系。我们还使用受试者工作特征曲线研究了p-tau217根据脑脊液区分淀粉样蛋白阳性和阴性受试者的能力。

结果

血浆p-tau217与脑脊液Aβ42/Aβ40显著相关（Rho = -0.75；p值<0.001）、p-tau181（r = 0.66；p值<0.001）和总tau（t-tau，r = 0.59；p值<0.001）。血浆NfL与脑脊液NfL相关（r = 0.48；p值<0.001）。按临床诊断，AD患者的血浆p-tau217水平高于健康对照（差值 = 0.63 pg/ml；p值<0.001）、额颞叶痴呆（FTD，差值 = 0.60 pg/ml；p值<0.001）和非退行性痴呆（差值 = 0.61 pg/ml；p值<0.001）。血浆p-tau217区分A+和A-受试者的曲线下面积为0.95（95%CI 0.93 - 0.97）。

结论

在临床环境中，血浆p-tau217在检测脑水平淀粉样蛋白病理方面显示出优异结果，AUC为0.95。它是AD的高度特异性标志物，并在疾病进程中逐渐升高。将血浆p-tau217用作初始诊断工具，设定敏感度和特异度为95%或97.5%的临界值，可节省57.4 - 84.8%的腰椎穿刺/正电子发射断层扫描（LP/PET），诊断准确率为95 - 97%。血浆NfL在不同认知阶段逐渐升高。