Naturally occurring alpha-synuclein autoantibodies in Parkinson's disease: Sources of (Error) variance in biomarker assays

Abstract

Alpha-synuclein (α -Syn) plays a pivotal role in the pathophysiology of Parkinson's disease (PD), which can partly be modulated by innate and adaptive immune functions, and vice versa. Here, naturally occurring α -Syn autoantibodies (α -SynnAbs) may be effective against α -Syn pathoetiology and may serve as a PD biomarker. However, serum and cerebrospinal fluid α -Syn-nAbs levels still lack consistent evidence as required for a reliable PD biomarker. Serum and cerebrospinal fluid α -Syn-nAbs levels of 66 PD patients and 69 healthy controls were assessed using a validated ELISA assay. Moreover, potential sources of error variance including unspecific ELISA background signals, free serum hemoglobin concentrations, α -Syn plate coating procedures, and differences in α -Syn-nAbs standards, were investigated. PD patients and controls did not differ in serum (p=.49) nor cerebrospinal fluid (p=.29) α -Syn-nAbs levels. Interestingly, free serum hemoglobin concentrations were negatively correlated with α -Syn-nAbs levels in controls (Spearman e=-.41, p