July 4, 2026Neurology1 citations
View Full PaperPutamen Dopamine Synthesis, Vesicular Storage, and Metabolism in Patients With Parkinson Disease
Key Points
- This research investigates how dopamine synthesis, storage, and metabolism vary between Parkinson disease and control groups.
- Evaluation of putamen dopamine levels using F-DOPA PET imaging.
- Comparison of dopamine-related intracellular reaction rates between patients with PD and controls.
- Estimation of reaction rates for synthesis, storage, release, reuptake, and metabolism.
- Findings indicate significant vesicular storage defects in dopaminergic terminals in PD compared to controls.
- Estimate of reaction rates reveals that vesicular uptake and leakage closely matched each other as the main functional abnormalities.
- Decreased vesicular uptake and increased leakiness were identified as key factors in putamen dopamine deficiency in PD.
Abstract
BACKGROUND AND OBJECTIVES: Putamen dopamine depletion characterizes Parkinson disease (PD). Intraneuronal processes determining dopamine stores have not been systematically examined. This study explored relative contributions of dopamine synthesis, storage, and metabolism to control-PD differences. METHODS: F-DOPA PET. RESULTS: F-DOPA-derived radioactivity compared with controls also indicated attenuated vesicular storage in PD. According to the complete model, control-PD differences in intraneuronal reaction rates were in descending order of vesicular uptake ≈ vesicular leakage > exocytotic release ≈ neuronal reuptake > L-aromatic-amino-acid decarboxylase activity ≈ TH activity > other reactions. DISCUSSION: Convergent quantitative evidence points to a substantial vesicular storage defect in residual dopaminergic terminals in PD. This finding challenges the sufficiency of nigrostriatal dopaminergic denervation alone to account for the biochemical phenotype of PD and highlights vesicular dopamine handling as a critical determinant of putamen dopamine deficiency. The reaction rate estimates were drawn from published point values rather than fitted to an experimental data set, and so conventional goodness-of-fit regression statistics were not conducted. Because of the assumption of steady-state conditions for calculating reaction rates based on equilibrium equations, the model does not address the dynamics of disease pathogenesis over years but does provide a platform for further extension to disease progression. BRIEF SUMMARY: We estimated rates of reactions involved with the synthesis, storage, release, reuptake, and metabolism of dopamine in the putamen in PD and found that the main intraneuronal functional abnormality separating PD from controls was attenuated vesicular sequestration, implicating decreased vesicular uptake through the vesicular monoamine transporter and increased vesicular leakiness as key determinants of putamen dopamine deficiency in PD.