Detection and assessment of alpha-synuclein in Parkinson disease

Different studies have reported varying alpha-synuclein values in the cerebrospinal fluid (CSF), serum, and plasma, making determination of the alpha-synuclein cutoff value for Parkinson's disease difficult and rendering identifying the cause of variation essential. We searched PubMed from inception to June 2021 and identified 76 eligible studies. Included studies reported data on total, phosphorylated, and oligomeric alpha-synuclein in the CSF, serum, or plasma from individuals with Parkinson's disease and healthy controls. The mean or median alpha-synuclein values from the included studies were summarized and categorized through laboratory assays to visualize potential trends. The enzyme-linked immunosorbent assay (ELISA) is the most common assay used to determine alpha-synuclein concentrations. Less common assays include Luminex, single molecule arrays, electrochemiluminescence, and immunomagnetic reduction (IMR). IMR is a single-antibody and wash-free immunoassay designed for determining the extremely low concentration of bio-molecules. For patients with Parkinson's disease, the median or mean testing values ranged from 60.9 to 55,000 pg/mL in the CSF, 0.446 to 1,777,100 pg/mL in plasma, and 0.0292 to 38,200,000 pg/mL in serum. The antibody selection was diverse between studies. The tendency of distribution was more centralized among studies that used the same kit. Studies adopting specific antibodies or in-house assays contribute to the extreme values. Only a few studies on phosphorylated and oligomeric alpha-synuclein were included. The type of assay and antibody selection in the laboratory played major roles in the alpha-synuclein variation. Studies that used the same assay and kit yielded relatively unanimous results. Furthermore, IMR may be a promising assay for plasma and serum alpha-synuclein quantification. A consensus on sample preparation and testing protocol unification is warranted in the future.