血浆Aβ42/40比值、磷酸化tau181、胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）在阿尔茨海默病和非阿尔茨海默病性痴呆连续病程中的诊断性能：一项国际多中心研究

Diagnostic performance of plasma Aβ42/40 ratio, p-tau181, GFAP, and NfL along the continuum of Alzheimer's disease and non-AD dementias: An international multi-center study.

作者信息

Doecke James D, Bellomo Giovanni, Vermunt Lisa, Alcolea Daniel, Halbgebauer Steffen, In 't Veld Sjors, Mattsson-Carlgren Niklas, Veverova Katerina, Fowler Christopher J, Boonkamp Lynn, Houtkamp Isabel M, Koel-Simmerlink Marleen, Verberk Inge M W, Gaetani Lorenzo, Toja Andrea, Wojdała Anna Lidia, Fortea Juan, Pijnenburg Yolande, Lemstra Afina, van der Flier Wiesje, Hort Jakub, Otto Markus, Hansson Oskar, Parnetti Lucilla, Masters Colin L, Lleó Alberto, González-Escalante Armand, Contador José, Suárez-Calvet Marc, Fernández-Lebrero Aida, Puig-Pijoan Albert, Ortiz-Romero Paula, Jiménez-Moyano Esther, Minguillón Carolina, Del Campo Marta, Teunissen Charlotte

机构信息

Australian E-Health Research Centre, CSIRO, Herston, Queensland, Australia.

Section of Neurology, Laboratory of Clinical Neurochemistry, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

出版信息

Alzheimers Dement. 2025 Jun;21(6):e14573. doi: 10.1002/alz.14573.

DOI:10.1002/alz.14573

PMID:40551285

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12185245/

Abstract

INTRODUCTION

Plasma phosphorylated tau (p-tau)181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and amyloid beta ratio (Aβ42/40) may have diagnostic and prognostic value in Alzheimer's disease (AD). Here we assess which markers can best identify AD from controls and other non-AD dementias in a large international multi-center study.

METHODS

Plasma samples (n = 1298) were collected from six international centers. Aβ40, Aβ42, GFAP, NfL, and p-tau181 were measured using single molecule array. In each group, AD diagnosis/co-pathology was defined according to cerebrospinal fluid biomarkers or amyloid positron emission tomography. Validations were performed in three separate cohorts via single and dual cut-off models.

RESULTS

p-tau181 showed the best area under the curve value to separate AD from frontotemporal dementia, controls, and Aβ- dementia with Lewy bodies. However, this discriminative power could not be reproduced by applying pre-defined cut-offs.

DISCUSSION

p-tau181 was the best single plasma marker for detecting AD at any stage. Specific cut-offs are needed to maximize diagnostic performances.

HIGHLIGHTS

Phosphorylated tau (p-tau)181 provided a clear differentiation between controls and Alzheimer's disease (AD) participants, with evidence of increased levels in the preclinical stage of AD. Plasma biomarkers demonstrated that when amyloid co-pathology is removed from dementia with Lewy bodies (DLB), only glial fibrillary acidic protein and neurofilament light chain remain to predict DLB. Given the low prevalence of amyloid co-pathology in frontotemporal dementia (FTD), p-tau181 and its ratio with amyloid beta 42 are strong biomarkers to differentiate FTD from AD.

摘要

引言

血浆磷酸化tau蛋白（p-tau）181、胶质纤维酸性蛋白（GFAP）、神经丝轻链（NfL）以及淀粉样β蛋白比值（Aβ42/40）在阿尔茨海默病（AD）中可能具有诊断和预后价值。在此，我们在一项大型国际多中心研究中评估哪些标志物能够最佳地将AD与对照以及其他非AD痴呆区分开来。

方法

从六个国际中心收集血浆样本（n = 1298）。使用单分子阵列检测Aβ40、Aβ42、GFAP、NfL和p-tau181。在每组中，根据脑脊液生物标志物或淀粉样蛋白正电子发射断层扫描定义AD诊断/合并病理学情况。通过单截断模型和双截断模型在三个独立队列中进行验证。

结果

p-tau181在将AD与额颞叶痴呆、对照以及路易体Aβ痴呆区分开来时，显示出最佳的曲线下面积值。然而，通过应用预定义的截断值无法再现这种区分能力。

讨论

p-tau181是在任何阶段检测AD的最佳单一血浆标志物。需要特定的截断值以最大化诊断性能。

要点

磷酸化tau蛋白（p-tau）181在对照与阿尔茨海默病（AD）参与者之间提供了明确的区分，有证据表明在AD临床前阶段其水平升高。血浆生物标志物表明，当从路易体痴呆（DLB）中去除淀粉样蛋白合并病理学情况时，只有胶质纤维酸性蛋白和神经丝轻链仍可用于预测DLB。鉴于淀粉样蛋白合并病理学情况在额颞叶痴呆（FTD）中的低患病率，p-tau181及其与淀粉样β蛋白42的比值是区分FTD与AD的强有力生物标志物。