Background: Multiple system atrophy(MSA) is a neurodegenerative disease characterized by intracellular α-synuclein deposits. There is an unmet need for blood-based biomarkers to diagnose MSA. Our previous studies have reported elevated α-synuclein levels in erythrocytes of MSA patients. However, α-synuclein protein in the membrane and cytoplasm of erythrocytes in MSA have not been investigated.
Methods: The membrane and cytoplasm were extracted from erythrocytes in 77 patients with MSA and 133 healthy controls. Levels of total and oligomeric α-synuclein were detected using Electrochemiluminescence assays. The correlations between α-synuclein levels and clinical characteristics were explored in MSA group. The diagnostic value of erythrocyte α-synuclein for MSA was determined by Receiver operator characteristic curve.
Results: α-synuclein levels in the erythrocyte membrane were significantly elevated in MSA patients compared with the healthy controls (total α-synuclein, p = 0.003; oligomeric α-synuclein/total α-synuclein, p = 0.033; oligomeric α-synuclein/protein, p < 0.001). The combination of total and oligomeric α-synuclein levels in erythrocyte membrane could efficiently distinguish MSA from healthy controls (sensitivity of 79.2%; specificity of 69.2%; area under the curve: 0.771). In contrast, no significant difference was found in erythrocyte cytoplasm α-synuclein levels. In the subgroup of 48 patients with probable MSA, there was a weakly negative correlation between oligomeric α-synuclein/protein in erythrocyte membrane and disease duration (r = -0.336; p = 0.009).
Conclusion: Our pilot study suggests that the membrane fraction of α-synuclein levels in erythrocyte were elevated in patients with MSA, and these levels may be decreased with the development of disease.
Keywords: Biomarker; Electrochemiluminescence; Erythrocyte cytoplasm; Erythrocyte membrane; Multiple system atrophy; SNCA; α-synuclein.
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