Objective: To comprehensively characterize central energy metabolism in Parkinson’s disease (PD) through cerebrospinal fluid (CSF) metabolomic profiling.
Background: We previously reported weight loss and systemic abnormalities in glycolysis and lipid metabolism in PD. However, central energy metabolic alterations remain unclear.
Method: CSF samples from 143 patients with PD and 57 controls were analyzed using LC-MS/MS for lactate, pyruvate, ketone bodies (acetoacetate, 3-hydroxybutyrate), acetate, and tricarboxylic acid (TCA) cycle intermediates. Associations with clinical indices were evaluated, adjusting for age and sex where appropriate.
Results: Acetoacetate was significantly elevated in PD (p<0.001) and correlated with greater motor severity (MDS-UPDRS Part3) and poorer cognitive performance (MMSE, ACE-R, MoCA-J, FAB), remaining significant after age and sex adjustment. CSF acetoacetate correlated with plasma levels, supporting peripheral-to-central metabolic coupling. In contrast, 3-hydroxybutyrate showed no difference between groups, suggesting altered mitochondrial redox dynamics. Although lactate levels were unchanged, the lactate/pyruvate ratio was significantly decreased (p<0.001), indicating a lower intracellular NADH/NAD⁺ ratio and a shift toward a more oxidized state rather than a simple alteration in glycolytic flux. Among TCA cycle intermediates, isocitrate increased (p=0.002) while malate was decreased (p<0.001), consistent with TCA cycle imbalance. Acetate levels were reduced in CSF (p<0.001), possibly reflecting enhanced central utilization of alternative substrates or altered transport dynamics.
Conclusion: PD is characterized by central metabolic alterations characterized by redox imbalance, TCA cycle disruption, and altered utilization of lipid-derived substrates, indicating a shift in energy metabolism. These findings provide mechanistic insight into PD pathophysiology and identify energy metabolism as a potential therapeutic target.
References: J Neurol Neurosurg Psychiatry. 2025 Nov 30:jnnp-2025-336929.
To cite this abstract in AMA style:
R. Nagao, Y. Mizutani, R. Ohdake, Y. Maeda, J. Yoshimoto, K. Kawabata, S. Shima, Y. Seino, M. Ito, A. Suzuki, H. Watanabe. Cerebrospinal Fluid Metabolic Alterations Reveal a Central Energy Metabolism Shift in Parkinson’s Disease [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/cerebrospinal-fluid-metabolic-alterations-reveal-a-central-energy-metabolism-shift-in-parkinsons-disease/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebrospinal-fluid-metabolic-alterations-reveal-a-central-energy-metabolism-shift-in-parkinsons-disease/