Objective: This study aimed to elucidate the associations between cerebrospinal fluid (CSF) cell-free mitochondrial DNA (cf-mtDNA) levels and body composition, nutritional status, and metabolic biomarkers in Parkinson’s disease (PD) to clarify its clinical significance as a biomarker of systemic energy metabolism.
Background: Recent studies suggest that patients with PD had lower levels of CSF cf-mtDNA compared to controls. However, its clinical relevance remains largely unexplored.
Method: This study enrolled 44 sporadic PD patients and 43 controls. Using a multiplex digital PCR assay, we quantified the levels of two regions of the mtDNA circular molecule (mt64-ND1 and mt96-ND5) in CSF, and calculated the mt96-ND5/mt64-ND1 ratio to estimate the extent of mtDNA deletions. We then analyzed their associations with clinical scores, body composition, nutritional markers, and plasma energy metabolism-related organic acids. Generalized linear models (GLMs) were applied to adjust for confounders.
Results: CSF mt64-ND1 and mt96-ND5 levels were significantly lower in PD patients than in controls (p = 0.002, p = 0.001), whereas the mt96-ND5/mt64-ND1 ratio showed no difference between the groups. GLM analysis identified body composition indices and serum albumin levels as major determinants of cf-mtDNA levels. Subgroup analysis revealed that PD patients with preserved body composition and nutritional status had lower cf-mtDNA levels. The mt96-ND5/mt64-ND1 ratio showed a biphasic association with body composition and an inverse correlation with plasma 2-ketoglutaric acid, a key energy metabolism intermediate.
Conclusion: CSF cf-mtDNA levels are reduced in PD and closely linked to body composition and nutritional status. The cf-mtDNA deletion ratio exhibits a complex relationship with body composition and correlates with 2-ketoglutaric acid. These findings suggest cf-mtDNA and its deletion ratio as potential biomarkers of systemic energy status and body composition in PD, warranting further research for clinical application.
To cite this abstract in AMA style:
Y. Mizutani, T. Nakai, Y. Maeda, R. Ohdake, R. Nagao, S. Shima, K. Kawabata, A. Ueda, M. Ito, H. Watanabe. CSF Mitochondrial DNA Indicates Body Composition and Energy Metabolism in Parkinson’s Disease. [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/csf-mitochondrial-dna-indicates-body-composition-and-energy-metabolism-in-parkinsons-disease/. Accessed November 20, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/csf-mitochondrial-dna-indicates-body-composition-and-energy-metabolism-in-parkinsons-disease/