Movement disorders : official journal of the Movement Disorder Society · 2025
Mitochondrial DNA Copy Number as a Potential Biomarker for the Severity of Motor Symptoms and Prognosis in Parkinson's Disease.
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Jo Sungyang, Oh Ji-Hye, Lee Eun-Jae, Choi Moongwan, Lee Jihyun, Lee Sangjin, Kim Tae Won, Sung Chang Ohk, Chung Sun Ju
Аннотация
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.
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.