Mitochondrial DNA copy number as a potential biomarker for the severity of motor symptoms and prognosis in Parkinson's disease

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The paper titled “Mitochondrial DNA Copy Number as a Potential Biomarker for the Severity of Motor Symptoms and Prognosis in Parkinson’s Disease” investigates whether mitochondrial DNA copy number (mtDNA-CN), measured from peripheral blood, can serve as a biomarker for both disease severity and progression in Parkinson’s disease (PD). 

Mitochondria play a central role in cellular energy production, and mitochondrial dysfunction has been strongly implicated in PD pathogenesis. The number of mitochondrial DNA copies within a cell (mtDNA-CN), an easily measurable indicator of mitochondrial function, has been implicated in various neurodegenerative diseases such as PD and Alzheimer’s disease. However, its clinical significance in relation to motor and cognitive outcomes in PD remained to be fully clarified. 

The primary aim of this study was to assess whether blood mtDNA-CN is associated with PD diagnosis, motor symptom severity, and future cognitive decline. This is particularly important, as identifying reliable, minimally invasive biomarkers could enhance risk stratification, aid early intervention, and inform clinical trial design. 

Using whole genome sequencing (WGS), we quantified mtDNA-CN from blood samples of 405 PD patients and 200 healthy controls (HC). We demonstrated that mtDNA-CN was significantly lower in PD patients compared to controls. Moreover, reduced mtDNA-CN correlated with greater motor symptom severity, as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS). Importantly, in a subgroup of patients with early PD (within 3 years of diagnosis), lower mtDNA-CN was predictive of an increased risk of developing dementia over a median 5-year follow-up. These findings remained robust after adjustment for potential confounders. 

Notably, mtDNA-CN was not significantly associated with future motor progression as measured by Hoehn and Yahr stage, suggesting that while mtDNA-CN reflects baseline motor impairment and dementia risk, it may not capture all aspects of motor progression. 

Our study suggests that blood mtDNA-CN may help diagnose PD and identify patients at higher risk for dementia. Our next steps will include long-term studies and repeated measurements of mtDNA-CN to see how it changes over time in relation to disease progression. Our goal is to eventually bring this type of personalized, biology-based monitoring into regular clinical care for PD patients. 

Read the paper

 

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