Increased bilirubin levels in Parkinson's disease

Abstract

Introduction: Oxidative stress plays a key role in Parkinson's disease (PD) etiopathology. Heme oxygenase, an important enzyme which regulates oxidative balance, converts heme molecules into carbon monoxide, iron and biliverdin/bilirubin. The role of bilirubin has not been fully studied in PD, showing controversial results over the last few decades. Our aim was to investigate the relationship between bilirubin levels and PD. Secondly, we sought to evaluate the link between bilirubin concentration with PD progression, severity and dopaminergic treatment.

Methods: We included 420 PD patients (56% males, mean age: 64 ± 12 years) and 435 healthy controls (47% males, mean age: 58 ± 17 years). Bilirubin levels in both groups were compared using linear regression and multivariate analysis adjusted according to age and sex. Secondly, a case study with the PD cohort was carried out and bilirubin levels were correlated with current treatment, duration and severity of disease.

Results: Bilirubin levels were significantly higher in PD patients than in controls (PD: 0.56 ± 0.26 mg/dl, controls: 0.45 ± 0.22 mg/dl; p < 0.001). In PD patients, we demonstrated a negative correlation between bilirubin levels and disease duration (p < 0.05). Higher bilirubin concentrations were identified in PD patients with Hoehn & Yahr stage ≤3. No relationship between bilirubin and treatment was found in PD patients.

Conclusions: Increased bilirubin levels are particularly related to the first years of PD. Overexpression of oxidative enzymes could play an important role in PD etiology, leading to higher bilirubin levels in the early stages of PD.

Keywords: Bilirubin; Heme oxygenase 1; Parkinson's disease; Pathophysiology.