Cao Yongliang, Xu Yifei, Cao Meiqun, Chen Nan, Zeng Qingling, Lai Mitchell K P, Fan Dahua, Sethi Gautam, Cao Yongkai
Lingang Laboratory, Shanghai 200120, China.
Institute of Gastroenterology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China.
Ageing Res Rev. 2025 Jun;108:102739. doi: 10.1016/j.arr.2025.102739. Epub 2025 Mar 21.
Neurodegenerative diseases, such as Alzheimer's Disease (AD), Multiple Sclerosis (MS), Parkinson's Disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are increasingly prevalent as global populations age. Fluid biomarkers, derived from cerebrospinal fluid (CSF), blood, saliva, urine, and exosomes, offer a promising solution for early diagnosis, prognosis, and disease monitoring. These biomarkers can reflect critical pathological processes like amyloid-beta (Aβ) deposition, tau protein hyperphosphorylation, α-syn misfolding, TDP-43 mislocalization and aggregation, and neuronal damage, enabling detection long before clinical symptoms emerge. Recent advances in blood-based biomarkers, particularly plasma Aβ, phosphorylated tau, and TDP-43, have shown diagnostic accuracy equivalent to CSF biomarkers, offering more accessible testing options. This review discusses the current challenges in fluid biomarker research, including variability, standardization, and sensitivity issues, and explores how combining multiple biomarkers with clinical symptoms improves diagnostic reliability. Ethical considerations, future directions involving extracellular vehicles (EVs), and the integration of artificial intelligence (AI) are also highlighted. Continued research efforts will be key to overcoming these obstacles, enabling fluid biomarkers to become crucial tools in personalized medicine for neurodegenerative diseases.
随着全球人口老龄化，神经退行性疾病，如阿尔茨海默病（AD）、多发性硬化症（MS）、帕金森病（PD）和肌萎缩侧索硬化症（ALS）越来越普遍。源自脑脊液（CSF）、血液、唾液、尿液和外泌体的液体生物标志物为早期诊断、预后评估和疾病监测提供了一个有前景的解决方案。这些生物标志物可以反映关键的病理过程，如β-淀粉样蛋白（Aβ）沉积、tau蛋白过度磷酸化、α-突触核蛋白错误折叠、TDP-43错误定位和聚集以及神经元损伤，从而能够在临床症状出现之前很久就进行检测。基于血液的生物标志物，特别是血浆Aβ、磷酸化tau蛋白和TDP-43的最新进展表明，其诊断准确性与脑脊液生物标志物相当，提供了更便捷的检测选择。本文综述讨论了液体生物标志物研究当前面临的挑战，包括变异性、标准化和敏感性问题，并探讨了将多种生物标志物与临床症状相结合如何提高诊断可靠性。还强调了伦理考量、涉及细胞外囊泡（EVs）的未来方向以及人工智能（AI）的整合。持续的研究努力将是克服这些障碍的关键，使液体生物标志物成为神经退行性疾病个性化医疗中的关键工具。
