Mitochondrial D-loop region methylation differentiates Parkinson’s disease from atypical parkinsonism and Parkinson’s disease dementia

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss and α-synuclein aggregation. Epigenetic mechanisms, including mitochondrial DNA (mtDNA) methylation, have been implicated in PD pathogenesis. Methylation of the mitochondrial displacement loop (D-loop) region may play a role in neurodegenerative processes. This case study assessed D-loop methylation levels in peripheral blood samples from 37 patients with PD, 18 patients with Parkinson’s disease dementia (PD-D), 26 patients with atypical parkinsonism (APS), and 26 healthy controls (HC). Associations with clinical parameters, sex, and L-dopa treatment were analyzed. D-loop methylation levels were significantly reduced in patients with PD-D and APS compared to PD patients and HC. Methylation levels were not associated with disease duration, clinical variables, sex, or L-dopa treatment. Decreased mitochondrial D-loop methylation in PD-D and APS may reflect disease-specific epigenetic mechanisms rather than clinical characteristics or treatment effects. Parkinson’s disease is a brain disorder that mainly affects movement and can also cause problems with memory and thinking. Scientists think that small chemical changes in DNA may play a role in how the disease develops. This study focused on mitochondria, the parts of cells that produce energy. We examined a control region of mitochondrial DNA using blood samples from people with Parkinson’s disease, Parkinson’s disease dementia, atypical parkinsonism, and healthy individuals. We found that these DNA changes were lower in people with Parkinson’s disease dementia and atypical parkinsonism, but not in those with Parkinson’s disease alone. The changes were not related to sex, disease features, or Parkinson’s medications. These results suggest that mitochondrial DNA changes may be linked to specific Parkinson-related conditions rather than treatment effects. This information may help future research better understand and distinguish between different forms of Parkinson’s disease.