Several studies have investigated if the levels of α-
synuclein autoantibodies (α-syn AAb) differ in serum of
Parkinson's disease (PD) patients and healthy subjects. Reproducible differences in their levels could serve as a
biomarker for PD. The results of previous studies however remain inconclusive. With the largest sample size examined so far, we aimed to validate serum α-syn AAb levels as a
biomarker for PD and investigated the presence of AAbs against other
synucleins. We performed ELISA and immunoblots to determine
synuclein AAb levels in the serum of 295 subjects comprising 157 PD patients from two independent cohorts, 46 healthy subjects, and 92 patients with other
neurodegenerative disorders. Although serum α- and β-syn AAb levels were significantly reduced in patients with PD and other
neurodegenerative disorders as compared to controls, the AAb levels displayed high inter-and intra-cohort variability. Furthermore, α-syn AAb levels showed no correlation to clinical parameters like age, disease duration, disease severity, and gender, that might also be directed against beta- and gamma-syn. In conclusion, serum
synuclein AAb levels do allow the separation of PD from healthy subjects but not from other
neurodegenerative disorders. Thus,
synuclein AAbs cannot be regarded as a reliable
biomarker for PD.