Peripheral Blood Mononuclear Cell Mitochondrial Bioenergetics Is Impaired in De Novo Parkinson's Disease

Abstract

Mitochondrial dysfunction is increasingly recognized as a key driver of pathology in patients with Parkinson's disease (PD). Peripheral blood mononuclear cells (PBMCs) have emerged as an accessible way to characterize mitochondrial function in PD. The aim of this study was to conduct a preliminary evaluation of the clinical relevance of PBMC mitochondrial function as a biomarker in early PD. PBMC mitochondrial bioenergetics were measured using the Seahorse XF platform in individuals with de novo, untreated PD (n = 13) and compared to age- and sex-matched healthy controls (n = 15). Correlations between mitochondrial endpoints and clinical outcomes were assessed in the PD group. Basal and ATP-linked respiration were elevated in the PD group (p = 0.002, p = 0.004), while spare capacity, or the cell's ability to handle an unexpected energetic stress, was decreased (p = 0.045), relative to controls. Notably, the variability within basal respiratory measurements was markedly increased in the PD group compared to controls (p = 0.002). Further analyses revealed significant correlations between spare capacity and clinical motor function scores within the PD group. These findings support the potential of PBMC bioenergetics as a biomarker for early-stage PD as well as disease progression.

Keywords: Mitochondrial function; PBMCs; Parkinson’s disease; Peripheral blood.