Ryan L Davis1, Siew L Wong1, Phillippa J Carling1, Thomas Payne1, Carolyn M Sue1, Oliver Bandmann1. 1. Department of Neurogenetics (RLD, CMS), University of Sydney, Kolling Institute and Royal North Shore Hospital, St Leonards, Sydney, New South Wales, Australia; Department of Neuroscience (SLW, PJC, TP, OB), Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom; and Department of Neurology (CMS), Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, Sydney, New South Wales, Australia.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLASSIFICATION OF EVIDENCE: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLASSIFICATION OF EVIDENCE: 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.
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