Blood mtDNA markers of mitochondrial subtype and early-onset Parkinson's disease biology - PubMed
5 hours ago
- #Parkinson's disease
- #Mitochondrial biomarkers
- #mtDNA deletions
- Mitochondrial dysfunction is central to Parkinson's disease (PD), linking genetic and environmental factors, necessitating blood-based mitochondrial biomarkers.
- The study analyzed somatic mtDNA major arc deletions, 7S DNA abundance, and copy number in blood (n=776) and CSF (n=72) from PD patients, at-risk individuals, converters, mitochondrial disease patients, and controls.
- Strongest blood effects were in PINK1/PRKN-PD and early-onset idiopathic PD, with high-risk prodromal individuals and converters showing alterations prior to diagnosis.
- In CSF-derived extracellular vesicles, age-associated increase in mtDNA copy number was observed in healthy controls but absent in idiopathic PD.
- Higher mtDNA deletion burden and lower 7S DNA correlated with higher risk of cognitive impairment and depression, and longer time to postural instability in PD patients.
- Combining mtDNA measures with mitochondrial polygenic risk scores, alpha-synuclein seeding, and neurofilament light chain improved discrimination (AUC up to 0.96 vs. 0.66 alone), capturing distinct biological dimensions of PD.
- MtDNA damage markers, especially deletion burden, reflect mitochondrial dysfunction detectable in early PD stages and support patient stratification in a multimodal framework, though not as standalone diagnostics.