INTRODUCTION: Neuronal α-synuclein dyshomeostasis and aggregation are essential features of early Parkinson's disease, as seen in isolated REM sleep behavior disorder (iRBD). The link between these pathologies across body compartments remains unclear. Our aim was to assess correlations between α-synuclein aggregates in stool and urine with α-synuclein content in neuronally derived L1CAM extracellular vesicles (L1EVs) from serum in iRBD. METHODS: We conducted a cross-sectional study, analyzing concurrent biobank samples from 46 individuals with iRBD to quantify α-synuclein aggregates in stool and urine with surface-based fluorescence intensity distribution analysis (sFIDA) and α-synuclein content in L1EVs using electrochemiluminescence. RESULTS: Corrected for age and sex, α-synuclein concentrations in L1EVs significantly correlated with stool aggregate concentration. No significant correlation was observed between α-synuclein concentration in L1EVs and urine, nor between urine and stool aggregates. CONCLUSION: The correlation of serum and stool α-synuclein suggests shared or linked pathology across these compartments, whereas the urinary compartment may be pathophysiologically distinct in prodromal Parkinson's Disease.