To investigate the presence of abnormal α-synuclein ( α-Syn) deposition in red blood cells (RBCs) in patients with early-onset Parkinson’s disease (PD) and determine whether RBC-derived α-Syn could serve as a biomarker for early-onset PD. Methods: A total of 26 patients with early-onset PD (onset age< 50 years) were included in the early-onset PD group, and 30 age- and sex-matched healthy control participants were included in the control group (HCs). Demographic and clinical data were collected for all participants. The Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr (H-Y) scale, Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA) were used to assess the patients in the early-onset PD group. Electrochemiluminescence immunoassay was performed to measure the levels of α-Syn monomers and aggregates in the RBCs of both groups. The correlation between RBC-derived α-Syn levels and clinical indicators in patients with early-onset PD was analyzed. Results: The levels of both α-Syn monomers and aggregates in RBCs were significantly higher in patients with early-onset PD than in HCs (P=0.009, P<0.0001). In terms of diagnostic performance, RBC-derived α-Syn aggregates showed superior performance over monomers, with an area under the receiver operating characteristic curve (AUC) of 0.887 (95% CI 0.794-0.981), 73.3% sensitivity, and 96.2% specificity for diagnosing early-onset PD. The levels of RBC-derived α-Syn monomers and aggregates showed no significant correlation with patient age, disease duration, H-Y stage, MDS-UPDRS III score, MMSE score, or MoCA score (P>0.05). Conclusion: Abnormal α-Syn deposition was found in the RBCs of patients with early-onset PD. RBC-derived α-Syn, particularly α-Syn aggregates, could serve as a biomarker for early-onset PD.