Significance and confounders of peripheral DJ-1 and alpha-synuclein in Parkinson's disease

Abstract

DJ-1 and alpha-synuclein are leading biomarkers for Parkinson's disease diagnosis and/or monitoring disease progression. A few recent investigations have determined DJ-1 and alpha-synuclein levels in plasma or serum, a more convenient sample source than cerebrospinal fluid; but the results were variable or even contradictory. Besides limitations in detection technology and limited number of cases in some studies, inadequate control of several important confounders likely has contributed to these inconsistent results. In this study, the relative contribution of each blood component to blood DJ-1 and alpha-synuclein was evaluated, followed by quantification of plasma levels of both markers in a larger cohort of patients/subjects ( approximately 300 cases) whose cerebrospinal fluid DJ-1 and alpha-synuclein levels have been determined recently. The results demonstrated that the DJ-1 and alpha-synuclein in blood resided predominantly in red blood cells (>95%), followed by platelets (1-4%), white blood cells and plasma (< or =1%), indicating that variations in hemolysis and/or platelet contamination could have a significant effect on plasma/serum DJ-1 and alpha-synuclein levels. Nonetheless, after adjusting for the age, although there was a trend of decrease in DJ-1 and alpha-synuclein in patients with Parkinson's or Alzheimer's disease compared with healthy controls, no statistical difference was observed in this cohort between any groups, even when the extent of hemolysis and platelet contamination were controlled for. Additionally, no correlation between DJ-1 or alpha-synuclein and Parkinson's disease severity was identified. In conclusion, unlike in cerebrospinal fluid, total DJ-1 or alpha-synuclein in plasma alone is not useful as biomarkers for Parkinson's disease diagnosis or progression/severity.