To study dopamine transporter (DAT) and tyrosine hydroxylase (TH) expression and function in the peripheral mononuclear cells (PBMCs) of patients with Parkinson’s disease (PD) compared to healthy controls. 

PD is characterized by progressive loss of dopamine in the substantia nigra. Previously, we described that peripheral immune cells express DAT and TH using flow cytometry. The PBMCs constitutively express DAT and TH with >90% of monocytes expressing both markers. We hypothesize that PBMCs of PD patients exhibit dysregulation in the dopamine homeostasis compared to healthy controls.

61 (38 male) PD patients and 35 healthy controls were enrolled in the study. PBMCs were isolated from blood samples of each study participant. Immunophenotyping was performed with flow cytometry using markers of mononuclear cells (CD14) and dopaminergic proteins DAT and TH. DAT-mediated uptake in monocyte-derived macrophages (MDMs) and membrane localization was also analyzed using live cell fluorescence microscopy and western blot.

Both DAT and TH were elevated in PBMCs of PD patients (21%) compared to healthy controls (17%) ( P<0.05). This change was seen irrespective of the treatment modality, with the highest increase in DAT/TH+ monocytes (50%) in drug naïve patients (n=5, P<0.05). Live cell fluorescence microscopy and biochemical analysis confirmed elevated DAT-mediated substrate uptake and increased membrane localization in PD MDMs (p<0.0001, n=5).

Our data indicate that peripheral dopamine homeostasis is dysregulated in the peripheral immune cells regardless of disease stage and treatment in patients with PD. This presents monocyte DAT/TH expression as a potential biomarker for PD and suggests that the peripheral dopamine system may be functionally linked to the central dopamine system. Future work will aim to validate this as a biomarker and investigate the mechanistic connection between peripheral and central dopamine systems.