中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (12): 3553-3563.doi: 10.4103/NRR.NRR-D-24-00599

• 原著:退行性病与再生 • 上一篇    下一篇

血浆循环游离DNA完整性和相对端粒长度作为帕金森病和多系统萎缩的诊断生物标志物：横断面研究

  

  • 出版日期:2025-12-15 发布日期:2025-03-17
  • 基金资助:
    该研究受国家重点研发计划（2021YFC2501205）、科技创新2030项目-“脑科学与类脑研究”重大项目（2021ZD0201101）、国家自然科学基金（82201409、82201401）和首都医科大学宣武医院青年培育项目（QNPY2021011）的资助。

Plasma circulating cell–free DNA integrity and relative telomere length as diagnostic biomarkers for Parkinson’s disease and multiple system atrophy: a cross-sectional study

Chao Ying1, 2, 3, 4, #, Chao Han4, #, Yuan Li5, #, Mingkai Zhang5 , Shuying Xiao5 , Lifang Zhao6 , Hui Zhang5 , Qian Yu7 , Jing An4 , Wei Mao5, *, Yanning Cai1, 2, 3, 4, 6, *   

  1. 1 Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing, China;  2 Beijing Municipal Geriatric Medical Research Center, Beijing, China;  3 Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing Key Laboratory of Parkinson’s Disease, Parkinson’s Disease Center for Beijing Institute on Brain Disorders, Clinical and Research Center for Parkinson’s Disease, Capital Medical University, Beijing, China;  4 National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China;  5 Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China;  6 Department of Clinical Biobank and Central Laboratory, Xuanwu Hospital, Capital Medical University, Beijing, China;  7 School of Health Professions, Stony Brook University, Stony Brook, NY, USA
  • Online:2025-12-15 Published:2025-03-17
  • Contact: Wei Mao, MD, PhD, wei.mao@ccmu.edu.cn; Yanning Cai, PhD, yanningcaimailbox@163.com.
  • Supported by:
    This work was supported by the National Key Research and Development Program of China, No. 2021YFC2501205 (to YC); the Science and Technology Innovation 2030 project, No. 2021ZD0201101 (to YC); the National Natural Science Foundation of China, Nos. 82201409 (to YL), 82201401 (to CH); and the Xuanwu Youth Development Project, No. QNPY2021011 (to CH).

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摘要：

帕金森病和多系统萎缩都被归类为α-突触核蛋白病，其特征是α-突触核蛋白的异常积聚，这为它们的比较研究提供了共同的病理背景。此外，帕金森病和多系统萎缩都涉及神经元死亡，这一过程可能会将循环游离DNA释放到血液中，导致其特征的特定改变。这一前提为研究循环游离DNA作为潜在生物标志物奠定了基础。循环游离DNA因其潜在的病理意义而受到关注，但其在帕金森病和多系统萎缩背景下的特征尚不完全清楚。此研究分析了62例帕金森病和33例多系统萎缩患者的血浆循环游离DNA特征，包括循环游离DNA总浓度、非凋亡来源的循环游离DNA水平、循环游离DNA完整性和相对端粒长度（cell free DNA relative telomere length, cf-RTL），以76名健康者为正常对照组。结果显示，与NC相比，帕金森病和多系统萎缩患者的循环游离DNA完整性显著提高，而相对端粒长度显著缩短。ROC分析表明，循环游离DNA完整性和相对端粒长度在区分帕金森病和多系统萎缩与正常对照组方面具有良好的诊断准确性。具体而言，较高的循环游离DNA完整度与帕金森病（OR: 5.72；95% CI: 1.54-24.19）和多系统萎缩（OR: 10.10；95% CI: 1.55-122.98）的风险增加有关。相反，较长的相对端粒长度与帕金森病（OR: 0.16；95% CI: 0.04-0.54）和多系统萎缩（OR:0.10；95% CI：0.01-0.57）的风险降低有关。这些结果表明，血浆循环游离DNA完整性和相对端粒长度在帕金森病和多系统萎缩中的诊断潜力，表明这些特性不仅可作为早期辅助诊断的生物标志物，还可能反映疾病的潜在病理机制。

https://orcid.org/0000-0002-7690-9013 (Wei Mao); https://orcid.org/0000-0003-0879-9809 (Yanning Cai)

关键词: 生物标志物, 循环游离DNA, 诊断, 多系统萎缩, 神经退行性疾病, 帕金森病, 风险因素

Abstract: In clinical specialties focusing on neurological disorders, there is a need for comprehensive and integrated non-invasive, sensitive, and specific testing methods. Both Parkinson’s disease and multiple system atrophy are classified as α-synucleinopathies, characterized by abnormal accumulation of α-synuclein protein, which provides a shared pathological background for their comparative study. In addition, both Parkinson’s disease and multiple system atrophy involve neuronal death, a process that may release circulating cell–free DNA (cfDNA) into the bloodstream, leading to specific alterations. This premise formed the basis for investigating cell–free DNA as a potential biomarker. Cellfree DNA has garnered attention for its potential pathological significance, yet its characteristics in the context of Parkinson’s disease and multiple system atrophy are not fully understood. This study investigated the total concentration, nonapoptotic level, integrity, and cellfree DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants, comprising 76 normal controls, 62 patients with Parkinson’s disease, and 33 patients with multiple system atrophy. In our cohort, 75.8% of patients with Parkinson’s disease (stage 1–2 of Hoehn & Yahr) and 60.6% of patients with multiple system atrophy (disease duration less than 3 years) were in the early stages. The diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic (ROC) analysis, and their association with disease prevalence was examined through logistic regression models, adjusting for confounders such as age, sex, body mass index, and education level. The results showed that cell-free DNA integrity was significantly elevated in both Parkinson’s disease and multiple system atrophy patients compared with normal controls (P < 0.001 for both groups), whereas cell-free DNA relative telomere length was markedly shorter (P = 0.003 for Parkinson’s disease and P = 0.010 for multiple system atrophy). Receiver operating characteristic analysis indicated that both cell-free DNA integrity and cell-free DNA relative telomere length possessed good diagnostic accuracy for differentiating Parkinson’s disease and multiple system atrophy from normal controls. Specifically, higher cell-free DNA integrity was associated with increased risk of Parkinson’s disease (odds ratio [OR]: 5.72; 95% confidence interval [CI]: 1.54–24.19) and multiple system atrophy (OR: 10.10; 95% CI: 1.55–122.98). Conversely, longer cell-free DNA relative telomere length was linked to reduced risk of Parkinson’s disease (OR: 0.16; 95% CI: 0.04–0.54) and multiple system atrophy (OR: 0.10; 95% CI: 0.01–0.57). These findings suggest that cell-free DNA integrity and cellfree DNA relative telomere length may serve as promising biomarkers for the early diagnosis of Parkinson’s disease and multiple system atrophy, potentially reflecting specific underlying pathophysiological processes of these neurodegenerative disorders.

Key words: biomarkers, cell-free DNA, diagnosis, multiple system atrophy, neurodegenerative diseases, Parkinson’s disease, risk factors