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Medical Research Center, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar.
Medical Education, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar.
Biology (Basel). 2025 Jan 26;14(2):129. doi: 10.3390/biology14020129.
Neurodegenerative disorders (NDs) cause progressive neuronal loss and are a significant public health concern, with NDs projected to become the second leading global cause of death within two decades. Huntington's disease (HD) is a rare, progressive ND caused by an autosomal-dominant mutation in the huntingtin () gene, leading to severe neuronal loss in the brain and resulting in debilitating motor, cognitive, and psychiatric symptoms. Given the complex pathology of HD, biomarkers are essential for performing early diagnosis, monitoring disease progression, and evaluating treatment efficacy. However, the identification of consistent HD biomarkers is challenging due to the prolonged premanifest HD stage, HD's heterogeneous presentation, and its multiple underlying biological pathways. This study involves a 10-year bibliometric analysis of HD biomarker research, revealing key research trends and gaps. The study also features a comprehensive literature review of emerging HD biomarkers, concluding the need for better stratification of HD patients and well-designed longitudinal studies to validate HD biomarkers. Promising candidate wet HD biomarkers- including neurofilament light chain protein (NfL), microRNAs, the mutant HTT protein, and specific metabolic and inflammatory markers- are discussed, with emphasis on their potential utility in the premanifest HD stage. Additionally, biomarkers reflecting brain structural deficits and motor or behavioral impairments, such as neurophysiological (e.g., motor tapping, speech, EEG, and event-related potentials) and imaging (e.g., MRI, PET, and diffusion tensor imaging) biomarkers, are evaluated. The findings underscore that the discovery and validation of reliable HD biomarkers urgently require improved patient stratification and well-designed longitudinal studies. Reliable biomarkers, particularly in the premanifest HD stage, are crucial for optimizing HD clinical management strategies, enabling personalized treatment approaches, and advancing clinical trials of HD-modifying therapies.
神经退行性疾病（NDs）会导致神经元进行性丧失，是一个重大的公共卫生问题，预计在二十年内NDs将成为全球第二大主要死因。亨廷顿舞蹈症（HD）是一种罕见的进行性神经退行性疾病，由亨廷顿（HTT）基因的常染色体显性突变引起，导致大脑中严重的神经元丧失，并产生使人衰弱的运动、认知和精神症状。鉴于HD复杂的病理学特征，生物标志物对于早期诊断、监测疾病进展以及评估治疗效果至关重要。然而，由于HD临床前期阶段较长、临床表现异质性以及其多种潜在生物学途径，确定一致的HD生物标志物具有挑战性。本研究对HD生物标志物研究进行了为期10年的文献计量分析，揭示了关键的研究趋势和差距。该研究还对新兴的HD生物标志物进行了全面的文献综述，得出结论认为需要对HD患者进行更好的分层，并开展精心设计的纵向研究以验证HD生物标志物。文中讨论了有前景的候选HD生物标志物，包括神经丝轻链蛋白（NfL）、微小RNA、突变型HTT蛋白以及特定的代谢和炎症标志物，重点强调了它们在HD临床前期阶段的潜在用途。此外，还对反映脑结构缺陷以及运动或行为障碍的生物标志物进行了评估，如神经生理学（如运动轻敲、言语、脑电图和事件相关电位）和影像学（如磁共振成像、正电子发射断层扫描和扩散张量成像）生物标志物。研究结果强调，可靠的HD生物标志物的发现和验证迫切需要改善患者分层和精心设计的纵向研究。可靠的生物标志物，尤其是在HD临床前期阶段，对于优化HD临床管理策略、实现个性化治疗方法以及推进HD修饰疗法的临床试验至关重要。
