Plasma p-tau217 and p-tau217/Aβ1-42 are effective biomarkers for identifying CSF- and PET imaging-diagnosed Alzheimer's disease: Insights for research and clinical practice

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-01-30 DOI:10.1002/alz.14536

Xiaomei Zhong, Qiang Wang, Mingfeng Yang, Gaohong Lin, Kexin Yao, Zhangying Wu, Danyan Xu, Huarong Zhou, Ben Chen, Haishan Shi, Min Zhang, Xiaolei Shi, Yijie Zeng, Jingyi Lao, Shuang Liang, JiaFu Li, Qin Liu, Huanmin Liu, Yunheng Chen, Yicheng Lin, Cong Ouyang, Jieqin Lv, Xiang Liang, Yuwang Cheng, Pengcheng Ran, Baoying Gong, Bin Zhang, Jianwen Guo, Hong Zhang, Sen Liu, Jihui Zhang, Haiying Liu, Yuping Ning

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引用次数: 0

Abstract

INTRODUCTION

With the advancement of disease-modifying therapies for Alzheimer's disease (AD), validating plasma biomarkers against cerebrospinal fluid (CSF) and positron emission tomography (PET) standards is crucial in both research and real-world settings.

METHODS

We measured plasma phosphorylated tau (p-tau)217, p-tau181, amyloid beta (Aβ)1-40, Aβ1-42, and neurofilament light chain in research and real-world cohorts. Participants were categorized by brain amyloid status using US Food and Drug Administration/European Medicines Agency–approved CSF or PET methods.

RESULTS

Plasma p-tau217 and p-tau217/Aβ1-42 demonstrated superior accuracy in detecting brain amyloid pathologies, with area under the curve from 0.94 to 0.97 in all cohorts. Specificity was lower in the real-world cohort but improved significantly by integrating demographic and clinical factors, aligning performance with research cohorts. Additionally, plasma biomarkers exhibited strong correlations with their CSF counterparts and PET standardized uptake value ratios, with significant associations in amyloid-positive participants.

DISCUSSION

Plasma p-tau217 and p-tau217/Aβ1-42 are effective diagnostic tools. However, patient demographics, apolipoprotein E ε4 status, and cognitive condition must be considered to improve specificity in the clinical practice.

Highlights

Plasma phosphorylated tau (p-tau)217 and p-tau217/amyloid beta (Aβ)1-42 demonstrated exceptional accuracy (area under the curve: 0.94–0.97) in detecting brain amyloid pathologies across both research (Southern China Aging Brain Initiative [SCABI]-1, SCABI-2) and real-world clinical practice (RCP) cohorts.
Incorporating patient-specific factors (sex, age, apolipoprotein E ε4, cognitive status) improved diagnostic specificity in the clinical RCP cohort, aligning its performance with that of research cohorts.
Plasma biomarkers, particularly p-tau217 and their ratios, showed robust correlations with cerebrospinal fluid biomarkers and positron emission tomography amyloid standardized uptake value ratios, underscoring their value as non-invasive diagnostic alternatives.
Plasma p-tau217 and p-tau217/Aβ1-42 proved highly effective in diagnosing amyloid burden, offering a practical solution to bridge research advancements with real-world clinical practice.

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血浆p - tau217和p - tau217/ a - β1 - 42是识别CSF和PET成像诊断的阿尔茨海默病的有效生物标志物：研究和临床实践的见解

随着阿尔茨海默病（AD）疾病修饰疗法的进步，验证血浆生物标志物对脑脊液（CSF）和正电子发射断层扫描（PET）标准的影响在研究和现实世界环境中都至关重要。方法：我们在研究和现实世界的队列中测量血浆磷酸化tau蛋白（p‐tau）217、p‐tau181、β淀粉样蛋白（Aβ）1‐40、Aβ1‐42和神经丝轻链。使用美国食品和药物管理局/欧洲药品管理局批准的CSF或PET方法根据脑淀粉样蛋白状态对参与者进行分类。结果血浆p - tau217和p - tau217/ a - β1 - 42在检测脑淀粉样蛋白病理方面表现出更高的准确性，在所有队列中曲线下面积为0.94 ~ 0.97。特异性在现实世界队列中较低，但通过整合人口统计学和临床因素，使研究队列的表现一致，特异性显著提高。此外，血浆生物标志物与其CSF对应物和PET标准化摄取值比表现出很强的相关性，在淀粉样蛋白阳性参与者中具有显著相关性。血浆p - tau217和p - tau217/ a - β1 - 42是有效的诊断工具。然而，在临床实践中，必须考虑患者人口统计学，载脂蛋白E ε4状态和认知状况，以提高特异性。血浆磷酸化tau蛋白（p‐tau）217和p‐tau蛋白/ β淀粉样蛋白（Aβ）1‐42在检测脑淀粉样蛋白病理方面表现出卓越的准确性（曲线下面积：0.94-0.97），这两项研究（华南脑衰老计划[SCABI]‐1，SCABI‐2）和现实世界的临床实践（RCP）队列。纳入患者特异性因素（性别、年龄、载脂蛋白ε4、认知状态）可提高临床RCP队列的诊断特异性，使其表现与研究队列一致。血浆生物标志物，特别是p - tau217及其比值，显示出与脑脊液生物标志物和正电子发射断层扫描淀粉样蛋白标准化摄取值比值的强相关性，强调了它们作为非侵入性诊断替代方案的价值。血浆p - tau217和p - tau217/ a - β1 - 42被证明在诊断淀粉样蛋白负担方面非常有效，为研究进展与现实世界的临床实践之间的桥梁提供了实用的解决方案。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.