中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (10): 4843-4853.doi: 10.4103/NRR.NRR-D-25-00759

• 综述:退行性病与再生 • 上一篇    下一篇

基于血液生物标志物与阿尔茨海默病的早期诊断

  

  • 出版日期:2026-10-15 发布日期:2026-06-12
  • 基金资助:
    国家自然科学基金(82272414)、山东省重点研发计划(2022CXGC010507)以及山东省泰山学者计划(tsqnz20240852)

Blood-based biomarkers and early diagnosis of Alzheimer’s disease.

Zhikang Cui1, Guixia Li2, Shuyong Wei3, Qian Cheng1, Qian Yu1, Shuai Zong1, Pengfei Zhang1, Hang Chen1, Shuyi Yu1, Shuang Wu4, Ming Li1, *, Zhiming Lu1, 4, *   

  1. 1Department of Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China; 
    2Department of Laboratory Medicine, Heze Municipal Hospital, Heze, Shandong Province, China; 
    3Xiajin County People’s Hospital, Dezhou, Shandong Province, China; 
    4Department of Laboratory Medicine, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China
  • Online:2026-10-15 Published:2026-06-12
  • Contact: Ming Li, MD, drmingli@yeah.net; Zhiming Lu, MD, luzhiming@sdu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82272414 (to ZL); the Key Research and Development Program of Shandong Province in China, No. 2022CXGC010507 (to ZL); and the Taishan Scholars Program of Shandong Province, No. tsqnz20240852 (to ML).

摘要:

阿尔茨海默病是一种常见神经退行性疾病,以进行性记忆丧失、认知功能下降及行为改变为特征。基于血液的生物标志物因其易获取性和成本效益,近年来备受关注。文章综述了阿尔茨海默病血液标志物在多个关键领域的最新进展:在早期诊断中,β-淀粉样蛋白和磷酸化tau蛋白等标志物可在临床症状出现前识别阿尔茨海默病;磷酸化tau蛋白217和神经丝轻链等生物标志物的动态变化可反映疾病进展,并与认知衰退呈正相关,从而实现阿尔茨海默病进程的持续监测。此外,磷酸化tau蛋白181和胶质纤维酸性蛋白等标志物通过区分阿尔茨海默病与额颞叶痴呆等其他痴呆症,辅助开展鉴别诊断。与神经修复相关的血脑屏障生物标志物(尤其是脑源性神经营养因子)为追踪神经再生和治疗反应开辟了新途径。单分子阵列和免疫沉淀质谱等先进检测技术显著提升了血脑屏障生物标志物的敏感性和特异性,加速了其临床转化进程。综上所述,血液生物标志物在改善阿尔茨海默病早期诊断、监测疾病进展、辅助鉴别诊断及评估治疗效果方面具有巨大潜力。文章全面评估了血液生物标志物的转化潜力,强调其临床实用价值,并为大规模应用指明未来方向。文章呼吁优先配置科研资源,加速基于血液的生物标志物向临床转化的进程,最终实现基于血液的生物标志物的阿尔茨海默病精准治疗。


https://orcid.org/0009-0002-9307-7009 (Ming Li); https://orcid.org/0000-0003-1228-5739 (Zhiming Lu)

关键词: 阿尔茨海默病, 淀粉样斑块, 生物标志物, 痴呆症, 早期诊断, 神经再生, 神经退行性疾病, 神经原纤维缠结, 神经炎症, 神经病理学

Abstract: Alzheimer’s disease is a common neurodegenerative disease characterized by progressive memory loss, cognitive decline, and behavioral changes. Blood-based biomarkers have recently gained significant attention due to their accessibility and cost-effectiveness. This review highlights the latest progress in multiple key areas of blood-based biomarkers for Alzheimer’s disease. For early diagnosis, blood-based biomarkers such as amyloid-β and phosphorylated tau can identify Alzheimer’s disease even before clinical symptoms emerge. Dynamic changes in blood-based biomarkers, including p-tau217 and neurofilament light chain, reflect disease progression and correlate with cognitive decline, enabling continuous monitoring of Alzheimer’s disease progression. Additionally, blood-based biomarkers such as p-tau181 and glial fibrillary acidic protein aid in differential diagnosis by distinguishing Alzheimer’s disease from other dementias such as frontotemporal dementia. Blood-based biomarkers related to nerve repair have opened up new avenues for tracking nerve regeneration and therapeutic response, especially brain-derived neurotrophic factor. Furthermore, advanced detection technologies such as single-molecule array and immunoprecipitation-mass spectrometry have significantly improved the sensitivity and specificity of blood-based biomarkers, facilitating their clinical translation. In summary, blood-based biomarkers hold strong potential to improve early diagnosis, monitor progression, differential diagnosis, and evaluate therapies in Alzheimer’s disease. This review provides a comprehensive and updated evaluation of the translational potential of blood-based biomarkers, emphasizing their practical utility in clinical settings and offering insights into future directions for large-scale application. This review emphasizes the need to prioritize the allocation of scientific resources, expedite the transition of blood-based biomarkers to clinical implementation, and ultimately achieve precise treatment of Alzheimer’s disease using these biomarkers.

Key words: Alzheimer’s disease, amyloid plaques, biomarkers, dementia, early diagnosis, nerve regeneration, neurodegenerative diseases, neurofibrillary tangles, neuroinflammation, neuropathology