Yang Ming, Zhang Allison, Chen Meng, Cao Jing
Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Department of Neurosurgery, The Cancer Hospital of the Chinese Academy of Medical Sciences, Beijing, China.
Ann Lab Med. 2025 Jul 1;45(4):381-390. doi: 10.3343/alm.2024.0611. Epub 2025 Jun 18.
Neurological disorders, including neurodegenerative diseases, traumatic brain injuries (TBI), and central nervous system (CNS) tumors, are complex conditions that significantly impact patients globally. Timely diagnosis and monitoring are critical for improving outcomes, driving the need for reliable biomarkers. Specifically, biomarkers detectable in cerebrospinal fluid (CSF) and blood offer important insights into disease presence and progression. This review explores the evolution of circulating blood biomarkers for neurodegenerative diseases, TBI, and CNS tumors, highlighting advanced detection technologies from enzyme-linked immunosorbent assays (ELISAs) to electrochemiluminescence (ECL) assays, single-molecule arrays (Simoa), and mass spectrometry. Advanced technologies with enhanced sensitivity and specificity, particularly in detecting low-abundance analytes, facilitate the investigation of CSF biomarkers for various neurological disorders. We also describe the progress in blood-based biomarkers for , emerging as less invasive alternatives to CSF sampling. Clinically, the implementation of Alzheimer's disease (AD) blood biomarkers Aβ/Aβ ratio and Apolipoprotein E isoform-specific peptide can aid the diagnosis, while p-tau181 and p-tau217 differentiates AD dementia from non-AD neurodegenerative diseases. Blood glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 are used in ruling out mild TBI. Despite these innovations, challenges remain, including assay standardization, sensitivity/specificity trade-offs, and the requirement for longitudinal studies to understand biomarker utility over time. Future research should focus on addressing these challenges to fully realize the potential of blood-based biomarkers in neurological disorder diagnostics and patient care.
神经系统疾病，包括神经退行性疾病、创伤性脑损伤（TBI）和中枢神经系统（CNS）肿瘤，是复杂的病症，在全球范围内对患者产生重大影响。及时诊断和监测对于改善治疗结果至关重要，这推动了对可靠生物标志物的需求。具体而言，可在脑脊液（CSF）和血液中检测到的生物标志物为疾病的存在和进展提供了重要见解。本综述探讨了用于神经退行性疾病、TBI和CNS肿瘤的循环血液生物标志物的演变，重点介绍了从酶联免疫吸附测定（ELISA）到电化学发光（ECL）测定、单分子阵列（Simoa）和质谱等先进检测技术。具有更高灵敏度和特异性的先进技术，特别是在检测低丰度分析物方面，有助于研究各种神经系统疾病的脑脊液生物标志物。我们还描述了基于血液的生物标志物的进展，它们作为脑脊液采样的侵入性较小的替代方法而出现。在临床上，阿尔茨海默病（AD）血液生物标志物Aβ/Aβ比率和载脂蛋白E异构体特异性肽的应用有助于诊断，而p-tau181和p-tau217可将AD痴呆与非AD神经退行性疾病区分开来。血液中的胶质纤维酸性蛋白和泛素C末端水解酶-L1用于排除轻度TBI。尽管有这些创新，但挑战仍然存在，包括检测标准化、灵敏度/特异性权衡以及需要进行纵向研究以了解生物标志物随时间的效用。未来的研究应专注于应对这些挑战，以充分实现基于血液的生物标志物在神经系统疾病诊断和患者护理中的潜力。
