Serum FGF-21, GDF-15, and blood mtDNA copy number are not biomarkers of Parkinson disease.

Abstract

Strong evidence of mitochondrial dysfunction exists for both familial and sporadic Parkinson disease (PD). A simple test, reliably identifying mitochondrial dysfunction, could be important for future stratified medicine trials in PD. We previously undertook a comparison of serum biomarkers in classic mitochondrial diseases and established that serum growth differentiation factor 15 (GDF-15) outperforms fibroblast growth factor 21 (FGF-21) when distinguishing patients with mitochondrial diseases from healthy controls. This study aimed to systematically assess serum FGF-21 and GDF-15, together with mitochondrial DNA (mtDNA) copy number levels in peripheral blood cells from patients with PD and healthy controls, to determine whether these measures could act as a biomarker of PD. One hundred twenty-one patients with PD and 103 age-matched healthy controls were recruited from a single center. Serum FGF-21 and GDF-15, along with blood mtDNA copy number, were quantified using established assays. There were no meaningful differences identified for any of the measures when comparing patients with PD with healthy controls. This highlights a lack of diagnostic sensitivity that is incompatible with these measures being used as biomarkers for PD. In this study, serum FGF-21, serum GDF-15, and blood mtDNA levels were similar in patients with PD and healthy controls and therefore unlikely to be satisfactory indicators of mitochondrial dysfunction in patients with PD. This study provides Class III evidence that serum FGF-21, serum GDF-15, and blood mtDNA copy number levels do not distinguish patients with PD from healthy controls. There was no diagnostic uncertainty between patients with PD and healthy controls.