Leukocytic Dopamine D2 Receptors as Biomarkers for Brain Dopamine Levels in Parkinson Disease

Having the ability to objectively index dopamine (DA) levels in the brain with a peripheral biomarker of brain DA would enable the objective monitoring of the progression of Parkinson disease (PD) and other DA-dependent disorders. This study investigates this potential biomarker using a DA-depletion approach, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin model and subjects with PD, which are well-known models of DA depletion in the midbrain of rodents and humans, respectively. MPTP-induced DA depletion in the substantia nigra compacta resulted in a significant decrease in DA and norepinephrine levels in the blood. The proportion of dopamine D2 receptor (D2R)-expressing leukocytes progressively decreased (specifically B and T cells) during the DA depletion. Subjects with PD displayed significantly decreased D2R expression in B and T cells, and increased levels in epinephrine, DA, norepinephrine, and levodopa, compared with control subjects. A significant negative correlation was found between blood levodopa and D2R expression in classical monocytes, which correlated mildly with blood DA levels. The modulation of peripheral D2Rs in PD and MPTP seen in this study demonstrates that substantia nigra compacta dopamine depletion in humans and rodents does manifest in the periphery. Although this study did not provide a clear narrative of how nigral and peripheral dopamine systems mirror each other, the results give evidence that peripheral D2Rs may be both biomarkers and important substrates for treatment of dopamine-dependent disorders.