Abstract
BackgroundErythrocytes are a major source of peripheral α-synuclein (α-Syn). The goal of the current investigation is to evaluate erythrocytic total, oligomeric/aggregated, and phosphorylated α-Syn species as biomarkers of Parkinson’s disease (PD). PD and healthy control blood samples were collected along with extensive clinical history to determine whether total, phosphorylated, or aggregated α-Syn derived from erythrocytes (the major source of blood α-Syn) are more promising and consistent biomarkers for PD than are free α-Syn species in serum or plasma.MethodsUsing newly developed electrochemiluminescence assays, concentrations of erythrocytic total, aggregated and phosphorylated at Ser129 (pS129) α-Syn, separated into membrane and cytosolic components, were measured in 225 PD patients and 133 healthy controls and analyzed with extensive clinical measures.ResultsThe total and aggregated α-Syn levels were significantly higher in the membrane fraction of PD patients compared to healthy controls, but without alterations in the cytosolic component. The pS129 level was remarkably higher in PD subjects than in controls in the cytosolic fraction, and to a lesser extent, higher in the membrane fraction. Combining age, erythrocytic membrane aggregated α-Syn, and cytosolic pS129 levels, a model generated by using logistic regression analysis was able to discriminate patients with PD from neurologically normal controls, with a sensitivity and a specificity of 72 and 68%, respectively.ConclusionsThese results suggest that total, aggregated and phosphorylated α-Syn levels are altered in PD erythrocytes and peripheral erythrocytic α-Syn is a potential PD biomarker that needs further validation.
Highlights
Erythrocytes are a major source of peripheral α-synuclein (α-Syn)
Establishment of the ECL assays To reliably quantify total, aggregated and phosphorylated at Ser129 (pS129) levels in human erythrocytes, specific and sensitive novel ECL methods were developed on the Meso Scale Discovery (MSD) platform
We found that pS129 significantly increased in erythrocytes of Parkinson’s disease (PD) patients, suggesting that aberrant phosphorylation of α-Syn may occur in peripheral blood, consistent with previous findings in plasma [21]
Summary
Erythrocytes are a major source of peripheral α-synuclein (α-Syn). The goal of the current investigation is to evaluate erythrocytic total, oligomeric/aggregated, and phosphorylated α-Syn species as biomarkers of Parkinson’s disease (PD). PD and healthy control blood samples were collected along with extensive clinical history to determine whether total, phosphorylated, or aggregated α-Syn derived from erythrocytes (the major source of blood α-Syn) are more promising and consistent biomarkers for PD than are free α-Syn species in serum or plasma. Previous studies have examined α-synuclein (α-Syn), a key protein critically involved in PD pathogenesis, as a potential biomarker. Most studies focus on cerebrospinal fluid (CSF) [2,3,4], which is in direct contact with the Because collection of peripheral blood samples is considerably easier, defining biomarkers in blood has numerous advantages. The interaction of α-Syn with lipid membranes is implicated in its physiological and pathological roles [15,16,17], and PD patients exhibit morphological abnormalities of
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
