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

• DOI: 10.1002/mds.30098
• Publication Date: 2025-01-06T13:48:53Z
• Authors: Sungyang Jo; Ji‐Hye Oh; Eun‐Jae Lee; Moongwan Choi; Jihyun Lee; Sangjin Lee; Tae Won Kim; Chang Ohk Sung; Sun Ju Chung

AbstractBackgroundMitochondrial 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.ObjectiveThis study aimed to assess the diagnostic and prognostic capabilities of mtDNA‐CN in PD.MethodsWe 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).ResultsmtDNA‐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.ConclusionOur 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.