VEGFA gene expression levels in patients with Parkinson’s disease and first-degree relatives

Abstract Background: Vascular endothelial growth factor A (VEGFA) contributes to angiogenesis and exerts neurotrophic and neuroprotective effects. Altered VEGFA expression has been implicated in neurodegenerative processes, including Parkinson´s disease (PD), yet findings from peripheral transcriptomic studies remain inconsistent. Data on individuals at increased risk, particularly first-degree relatives (FDRs), are limited. Objective: To evaluate peripheral blood VEGFA mRNA expression in patients with PD and their asymptomatic FDRs compared with healthy controls, and to assess age-related patterns and diagnostic performance. Methods: Peripheral blood VEGFA expression was analyzed in 123 participants (PD patients, FDRs, healthy controls) using one-step RT-qPCR normalized to B2M . Relative expression values were log-transformed (logVEGFA). Group differences, age correlations, and diagnostic discrimination were assessed using ANOVA, Pearson correlation, and receiver operating characteristic (ROC) analysis. Results: Both PD patients and FDRs showed significantly higher logVEGFA levels than healthy controls (p = 0.004), with the most pronounced differences observed in participants aged ≤ 60 years (p < 0.001). A positive correlation between age and logVEGFA was detected only in healthy controls. In participants aged ≤ 60 years, logVEGFA demonstrated excellent discrimination between PD patients and healthy individuals (AUC 0.897; 95% CI 0.771–1.000; sensitivity 100%, specificity 73.3%). Conclusions: Peripheral VEGFA expression is elevated in both PD patients and FDRs, particularly in younger individuals. Age-stratified VEGFA assessment may support early identification of individuals at risk of PD and complement existing prodromal biomarkers, pending longitudinal validation.