诊断学理论与实践

诊断学理论与实践 ›› 2026, Vol. 25 ›› Issue (02): 113-120.doi: 10.16150/j.1671-2870.2026.02.001

• 专家论坛 • 上一篇    下一篇

阿尔茨海默病诊断的血液生物标志物进展

方珉1, 刘静文2, 曾媛媛1, 金爱萍1()   

  1. 1 上海交通大学附属同仁医院神经内科， 上海 200336
    2 上海市第十人民医院神经内科， 上海 200072
  • 收稿日期:2025-09-22 修回日期:2025-11-23 接受日期:2025-11-24 出版日期:2026-04-25 发布日期:2026-04-25
  • 通讯作者: 金爱萍 E-mail：13402140058@163.com
  • 基金资助:
    国家自然科学基金面上项目(82471369);上海市脑健康青年基金-阿尔茨海默病精准诊疗研究项目

Progress in blood-based biomarkers for diagnosis of Alzheimer's disease

FANG Min1, LIU Jingwen2, ZENG Yuanyuan1, JIN Aiping1()   

  1. 1 Department of Neurology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
    2 Department of Neurology, Shanghai Tenth People's Hospital, Shanghai 200072, China
  • Received:2025-09-22 Revised:2025-11-23 Accepted:2025-11-24 Published:2026-04-25 Online:2026-04-25

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摘要：

阿尔茨海默病（Alzheimer’s disease，AD）作为全球老年认知症的首要病因，已成为严重的公共卫生挑战。然而，传统脑脊液（cerebrospinal fluid，CSF）检测和正电子发射断层显像（positron emission tomography，PET）技术因侵入性强、成本高和可及性有限，难以满足大规模人群筛查与分级诊疗需求，限制了AD早期诊断的普及。血液生物标志物（blood-based biomarkers，BBM）检测因无创、低成本和易于推广的优势，成为AD早期筛查与诊断的重要突破口。研究显示，血浆磷酸化tau蛋白（p-tau）和Aβ42/40比值等核心BBM在早期筛查和诊断中展现出较高应用价值。在初级保健环境中，p-tau217与Aβ42/40比值的组合（APS2）诊断AD的准确率达88%~92%，显著高于常规临床诊断（61%~73%）。在预测认知功能下降方面，血浆p-tau217的解释力（R²=0.33）已接近tau-PET（R²=0.34）。此外，BBM（如p-tau217）在监测抗Aβ单抗疗效和评估预后方面也显示出巨大潜力。然而，BBM的临床转化仍面临标准化检测、证据普适性、多因素干扰及伦理经济等严峻挑战。本文探讨BBM在临床诊疗中的实际应用，期望为BBM从研究向临床常规应用过渡提供循证依据，并为构建高效、可及的AD精准诊疗体系提供参考路径。

关键词: 阿尔茨海默病, 血液生物标志物, 早期筛查与诊断, 临床路径

Abstract:

Alzheimer's disease (AD), as the primary cause of dementia among the elderly globally, has become a serious public health challenge. However, traditional cerebrospinal fluid (CSF) testing and positron emission tomography (PET) are difficult to implement for large-scale population screening and tiered diagnosis due to their invasiveness, high cost, and limited accessibility, thereby limiting the widespread adoption of early diagnosis. Blood-based biomarkers (BBMs), with their advantages of being non-invasive, low-cost, and easily deployable, have become a crucial breakthrough for early AD screening and diagnosis. Studies have shown that core BBMs, such as plasma phosphorylated tau (p-tau) and the Aβ42/Aβ40 ratio, demonstrate high clinical value in early screening and diagnosis. In primary care settings, the combination of p-tau217 and the Aβ42/Aβ40 ratio (APS2) achieves a diagnostic accuracy of 88%-92% for AD, which is significantly higher than that of conventional clinical diagnosis (61%-73%). In predicting cognitive decline, the explanatory power of plasma p-tau217 (R²=0.33) is close to that of tau-PET (R²=0.34). Furthermore, BBMs (such as p-tau217) show great potential in monitoring the efficacy of anti-Aβ monoclonal antibodies and evaluating prognosis. Nevertheless, the clinical translation of BBMs still faces severe challenges, including assay standardization, evidence generalizability, multi-factor interference, and ethical and economic issues. This article explores the practical application of BBMs in clinical diagnosis and treatment, aiming to provide an evidence-based foundation for the transition of BBMs from research to routine clinical use and to offer a reference pathway for constructing an efficient, accessible, and precise AD diagnostic and therapeutic system.

Key words: Alzheimer's disease, Blood-based biomarkers, Early screening and diagnosis, Clinical pathway

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