Mitochondrial DNA Copy Number as a Potential Biomarker for the Severity of Motor Symptoms and Prognosis in Parkinson's Disease

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2025-01-06 DOI:10.1002/mds.30098

Sungyang Jo MD, PhD, Ji-Hye Oh PhD, Eun-Jae Lee MD, PhD, Moongwan Choi MD, Jihyun Lee MD, Sangjin Lee MD, Tae Won Kim MD, PhD, Chang Ohk Sung MD, PhD, Sun Ju Chung MD, PhD

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引用次数: 0

Abstract

Background

Mitochondrial function influences Parkinson's disease (PD) through the accumulation of pathogenic alpha-synuclein, oxidative stress, impaired autophagy, and neuroinflammation. The mitochondrial DNA copy number (mtDNA-CN), representing the number of mitochondrial DNA copies within a cell, serves as an easily assessable proxy for mitochondrial function.

Objective

This study aimed to assess the diagnostic and prognostic capabilities of mtDNA-CN in PD.

Methods

We assessed mtDNA-CN in blood samples using whole genome sequencing from 405 patients with PD and 200 healthy controls (HC). We examined the relationship between mtDNA-CN levels and motor symptom severity in PD, as well as their association with dementia development in patients with early-PD (within 3 years of diagnosis).

Results

mtDNA-CN levels were significantly lower in patients with PD compared with HC (P = 1.1 × 10⁻⁵). A negative correlation was discovered between mtDNA-CN level and motor severity in PD (correlation coefficient = −0.20; P = 0.008). Among 210 patients with early-PD, Cox regression analysis demonstrated an association between lower mtDNA-CN levels and a higher risk of developing dementia (hazard ratio [HR] = 0.41, 95% confidence interval: 0.20–0.86, P = 0.02), even after adjusting for age and blood cell count (HR = 0.41, 95% confidence interval: 0.18–0.92, P = 0.03). However, mtDNA-CN levels did not significantly correlate with motor progression in PD.

Conclusion

Our findings suggest that blood mtDNA-CN may function as a diagnostic biomarker for PD and a prognostic marker for dementia in patients with PD. © 2025 International Parkinson and Movement Disorder Society.

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线粒体DNA拷贝数作为帕金森病运动症状严重程度和预后的潜在生物标志物

背景：线粒体功能通过致病性α-突触核蛋白的积累、氧化应激、自噬功能受损和神经炎症对帕金森病（PD）产生影响。线粒体DNA拷贝数（mtDNA-CN）代表了细胞内线粒体DNA拷贝的数量，是线粒体功能的一个易于评估的替代指标：本研究旨在评估 mtDNA-CN 在帕金森病中的诊断和预后能力：我们使用全基因组测序技术评估了 405 名帕金森病患者和 200 名健康对照者（HC）血液样本中的 mtDNA-CN。结果：与健康对照组相比，帕金森病患者的 mtDNA-CN 水平明显较低（P = 1.1 × 10-5）。发现mtDNA-CN水平与帕金森病的运动严重程度呈负相关（相关系数=-0.20；P=0.008）。在 210 名早期帕金森病患者中，Cox 回归分析显示，即使调整了年龄和血细胞计数（HR = 0.41，95% 置信区间：0.18-0.92，P = 0.03），mtDNA-CN 水平越低，患痴呆症的风险越高（危险比 [HR] = 0.41，95% 置信区间：0.20-0.86，P = 0.02）。然而，mtDNA-CN水平与帕金森病的运动进展并无明显相关性：我们的研究结果表明，血液中的mtDNA-CN可作为帕金森病的诊断生物标志物和帕金森病患者痴呆症的预后标志物。© 2025 国际帕金森和运动障碍协会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.