Serum aromatic l-amino acid decarboxylase activity as a biomarker for prodromal and manifest Parkinson's disease

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BACKGROUND: Aromatic l-amino acid decarboxylase (AADC), or dopa decarboxylase (DDC), is a key enzyme in levodopa metabolism. Previous studies suggested that AADC protein levels may be increased in Parkinson's disease (PD), particularly if treated with levodopa in conjunction with a peripheral decarboxylase inhibitor (PDI). METHODS: Serum AADC enzyme activity was measured by quantifying ex vivo conversion of levodopa to dopamine, and correlated to diagnosis, disease stage and clinical parameters in (i) n = 43 people with probable prodromal PD; (ii) n = 592 people with early PD (≤5 years since diagnosis), of whom n = 116 unmedicated; (iii) n = 48 medicated people with PD with longer disease duration (>5 years); and (iv) n = 74 non-parkinsonian controls. FINDINGS: AADC activity was higher (P < 0.001) in probable prodromal PD (median 44.20 mU/L, IQR 34.30-58.60) and in manifest but unmedicated early PD (median 45.76, IQR 35.50-53.37) than in controls (median 35.09, IQR 26.92-44.49). Although AADC activity increased with disease duration (P < 0.001), there was no difference in AADC activity between probable prodromal and unmedicated manifest PD (P = 0.65). Use of dopaminergic medication increased AADC activity dose-dependently (median AADC in medicated PD: 110.09, IQR 85.44-145.82, P < 0.001). INTERPRETATION: People with PD have higher serum AADC activity than controls, even in prodromal and unmedicated stages, suggesting a process driven by dopaminergic neurodegeneration. In medicated people with PD, AADC activity is markedly and dose-dependently increased. Results suggest that increased AADC activity could serve as an early biomarker for disease in unmedicated patients and that use of dopaminergic medication paradoxically induces AADC. FUNDING: This study was funded by Stichting Alkemade-Keuls. Underlying cohorts were funded by Verily Life Sciences LLC, Radboud University Medical Center, Radboud University, the city of Nijmegen, the Province of Gelderland, ParkinsonNederland, the Dutch Digestive Foundation, Stichting Woelse Waard, Stichting Alkemade-Keuls, the Luxembourg National Research Fund (FNR), and the European Union's Horizon 2020 research and innovation programme.

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