Increased dimerization of alpha-synuclein in erythrocytes in Gaucher disease and aging

Abstract

Gaucher disease (GD) patients and carriers of glucocerebrosidase mutations are at an increased risk for Parkinson's disease (PD). The presynaptic protein alpha-synuclein (AS) is linked to PD. In the current work we examined biochemical properties of AS in GD patients. We generated membrane-enriched lysates from erythrocytes of 27 patients with GD and 32 age- and sex-matched controls and performed Western immunoblotting with antibodies against AS. Levels of monomeric AS did not differ between GD patients and controls and did not change as a function of age. However, the ratio of dimeric to monomeric AS was significantly increased in GD patients, and showed a significant positive correlation with age. Therefore, two major risk factors for PD, aging and GD status, are associated with an increased AS dimer to monomer ratio in erythrocytes. This ratio needs to be validated in further studies as a potential biomarker for PD risk.