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血浆p-tau217在伴有高发性脑血管疾病的亚洲队列中识别异常脑淀粉样蛋白负荷的临床效用

Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease.

作者信息

Chong Joyce R, Hilal Saima, Tan Boon Yeow, Venketasubramanian Narayanaswamy, Schöll Michael, Zetterberg Henrik, Blennow Kaj, Ashton Nicholas J, Chen Christopher P, Lai Mitchell K P

机构信息

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Memory, Aging and Cognition Centre, National University Health Systems, Singapore, Singapore.

出版信息

Alzheimers Dement. 2025 Feb;21(2):e14502. doi: 10.1002/alz.14502. Epub 2025 Jan 14.

Abstract

INTRODUCTION

Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance of a plasma immunoassay for tau phosphorylated at threonine 217 (p-tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based on a three-range reference, which stratified patients into low-, intermediate-, and high-risk groups for Aβ+.

METHODS

Brain amyloid status (Aβ- [n = 142] vs Aβ+ [n = 73]) on amyloid PET scans was assessed along with the plasma ALZpath p-tau217 assay to derive three-range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold).

RESULTS

Plasma p-tau217 (area under the curve [AUC] = 0.923) outperformed routine clinical assessments (AUC = 0.760-0.819; p ≤ 0.003) and other plasma biomarkers (AUC = 0.817-0.834; p < 0.001). The high-risk group showed significantly higher rates of cognitive decline than the low-risk group.

DISCUSSION

Risk stratification for PET Aβ+ based on a plasma p-tau217 assay demonstrated potential diagnostic and prognostic utility in an Asian cohort with concomitant CeVD.

HIGHLIGHTS

The utility of plasma p-tau217 to detect brain amyloid beta pathology (Aβ+) was studied in an Asian cohort with concomitant cerebrovascular disease Plasma tau phosphorylated at threonine 217 (p-tau217) showed superior utility in detecting Aβ+ compared to neuroimaging measures, clinical workup, or other blood biomarkers including p-tau181, glial fibrillary protein (GFAP), and Aβ Higher plasma p-tau217 correlated with faster cognitive decline Plasma p-tau217 shows promise as an Alzheimer's disease (AD) diagnostic and prognostic biomarker in diverse populations.

摘要

引言

我们利用一个伴有脑血管疾病(CeVD)高患病率的亚洲队列,基于一个三分位参考值评估了一种检测苏氨酸217位点磷酸化tau蛋白(p-tau217)的血浆免疫测定法在检测正电子发射断层扫描中的淀粉样β蛋白阳性(Aβ+)以及认知衰退方面的性能,该参考值将患者分为Aβ+的低、中、高风险组。

方法

在进行淀粉样蛋白PET扫描评估脑淀粉样蛋白状态(Aβ- [n = 142] 与Aβ+ [n = 73])的同时,进行血浆ALZpath p-tau217检测,以基于90%敏感性(下限)和90%特异性(上限)得出PET Aβ+的三分位参考点。

结果

血浆p-tau217(曲线下面积[AUC] = 0.923)优于常规临床评估(AUC = 0.760 - 0.819;p≤0.003)和其他血浆生物标志物(AUC = 0.817 - 0.834;p < 0.001)。高风险组的认知衰退率显著高于低风险组。

讨论

基于血浆p-tau217检测对PET Aβ+进行风险分层,在伴有CeVD的亚洲队列中显示出潜在的诊断和预后效用。

要点

在伴有脑血管疾病的亚洲队列中研究了血浆p-tau217检测脑淀粉样β蛋白病变(Aβ+)的效用 与神经影像学检查、临床检查或其他血液生物标志物(包括p-tau181、胶质纤维酸性蛋白[GFAP]和Aβ)相比,苏氨酸217位点磷酸化的血浆tau蛋白(p-tau217)在检测Aβ+方面表现出更优的效用 血浆p-tau217水平越高,认知衰退越快 血浆p-tau217有望成为不同人群中阿尔茨海默病(AD)的诊断和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ab/11848187/f3a4e36a9ee9/ALZ-21-e14502-g002.jpg

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