Synuclein in red blood cells: a potential biomarker for multiple system atrophy, and other updates on recent autonomic research

Excerpt

The search for a biomarker in the α-synucleinopathies and other neurodegenerative proteinopathies has become the “holy grail” of neurodegenerative research. Identifying a reliable biomarker could not only aid in diagnosis (e.g., differentiating Parkinson disease from multiple system atrophy [MSA]), but also in the prognosis (identifying those with more benign vs. severe forms of disease), and monitoring of disease progression (essential for future clinical trials), thus revolutionizing the field. Among the α-synucleinopathies, no disease presents more diagnostic and therapeutic challenges than MSA, the most aggressive subtype of these disorders. Various molecules, including α-synuclein (αSyn), DJ-1, tau, amyloid-β, neurofilament light chain, dopamine, and neuroinflammatory cytokines, have all been investigated as serum biomarkers for the diagnosis of MSA; however, sensitivity and specificity have been suboptimal due to interference by plasma proteins, contamination by hemolysis, and variations in detection methods. Interestingly, 99% of αSyn in whole blood is located in the red blood cells (RBCs). Because whole blood avoids the interference problems encountered when measuring cerebrospinal fluid and plasma αSyn, it could be an appealing option for the detection of pathological α-synuclein. There have now been several studies that have evaluated different forms of RBC-derived αSyn (e.g., total vs. the pathological phosphorylated subtype); however, because MSA is a rare disorder, studies have been limited by small sample sizes. …