Alpha-synuclein dimerization in erythrocytes of patients with genetic and non-genetic forms of Parkinson's Disease

Background: Variations of alpha-synuclein levels or species have been reported in Parkinson's Disease (PD). There has been little systematic examination of erythrocytes, a rich source of alpha-synuclein. Methods: Erythrocyte membranes were obtained from PD patients (mutation carriers in the a-synuclein gene (A53T-PD) and glucocerebrosidase gene (GBA-PD) (n = 18 each), and patients without known mutations (GUPD, n = 56)), and age-/sex-matched controls (n = 56). Levels of monomeric and dimeric alpha-synuclein were assessed using Western immunoblotting. Results: A statistically significant increase of alpha-synuclein dimer and dimer to monomer ratio was found in GBAPD and GU-PD. In contrast, dimer levels of A53T-PD were not different from controls. No difference was found in alpha-synuclein monomer levels. Conclusions: The increased alpha-synuclein dimer in GBA-PD and GU-PD is suggestive of an apparent systemic dysfunction causing the dimerization, and potentially oligomerization, of alpha-synuclein. These results may have implications for PD pathogenesis and biomarker development.