Bilirubin levels raised in newly diagnosed Parkinson’s disease

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Bilirubin levels are upregulated in patients with early Parkinson’s disease (PD) and are associated with disease progression at 2 years, a study shows.

The findings lend weight to the idea that serum bilirubin could serve as a biomarker for PD diagnosis and progression by reflecting a compensatory response to oxidative stress in the brain.

Researcher Paolo Barone, from the University of Salerno in Italy, and colleagues enrolled 75 newly diagnosed, drug-naïve PD patients and 75 matched controls in their study.

At baseline, they found that the mean bilirubin level was significantly higher among PD patients than controls at 0.74 mg/dL versus 0.51 mg/dL after correcting for age and gender.

The team found no association between baseline bilirubin levels and motor symptoms, evaluated via scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III. However, after 2 years, linear regression analysis showed that patients with higher bilirubin levels required significantly fewer dopaminergic drugs than those with lower levels, and tended to require a lower levodopa-equivalent daily dosage.

The team also found that, despite patients having similar motor scores during the off state, those with higher bilirubin levels had significantly lower motor scores during the on state. They say this finding is “intriguing” and could suggest an interaction between drug pharmacokinetics and bilirubin levels at the peripheral level.

However, the authors note that bilirubin levels were not associated with the change in UPDRS part III scores between baseline and 2 years. Nor did they find any relationship between nonmotor symptoms and bilirubin levels.

Writing in the European Journal of Neurology, the authors explain that bilirubin is a downstream product of heme oxygenase (HO), one of the body’s main anti-oxidative defences.

“[I]t is speculated that HO upregulation within the substantia nigra might be an adaptive response to increased oxidative stress occurring in PD and is likely to be responsible for increased bilirubin levels”, they write. Therefore, they suggest that the anti-oxidative response of HO could play an important role in preserving dopaminergic integrity.

They say theirs is the first study to specifically examine bilirubin levels in relation to PD progression.

“Further studies should be specifically addressed to evaluating variations in bilirubin levels during disease course and possible pathophysiological and clinical consequences”, they conclude.

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