Erythrocytic α-Synuclein Species for Parkinson's Disease Diagnosis and the Correlations With Clinical Characteristics

Abstract

Background: Erythrocytes contain most of the peripheral α-synuclein (α-syn), which is the key pathological molecular of α-synucleinopathies including Parkinson's disease (PD). Our objectives were to assess the efficiency of erythrocytic total and oligomeric α-syn levels as PD diagnostic biomarkers, and to identify the correlations between erythrocytic α-syn levels and physiological/psychiatrical assessment scales.

Methods: Home-brewed electrochemiluminescence assays were applied to assess the concentrations of erythrocytic total and oligomeric α-syn levels in a cohort including 124 patients with PD and 79 healthy controls (HCs). The correlations between erythrocytic α-syn levels and clinical measurements were assessed using Spearman's rank test.

Results: Both the erythrocytic total and oligomeric α-syn levels were significantly higher in PD patients than HCs. The biomarkers adjusted for age and sex discriminated PDs from HCs well with 80% sensitivity, 89% specificity and 79% sensitivity, 83% specificity, respectively. Combining erythrocytic total and oligomeric α-syn levels by using binary logistic regression analysis with the controlling of age and sex generated a factor discriminates PDs from HCs with 88% sensitivity and 85% specificity. The erythrocytic total but not oligomeric α-syn levels adjusted for age and sex significantly correlated with anxiety scales and the MDS-UPDRS III scales in PD patients, respectively.

Conclusion: We showed the usefulness of erythrocytic total and oligomeric α-syn levels as biomarkers for PD. Our results also suggest the capability of erythrocytic α-syn as a potential pathological factor and therapeutic target for psychiatric symptoms in PD patients.

Keywords: Parkinson’s disease; anxiety; depression; electrochemiluminescence; erythrocyte; α-syn.

FIGURE 1

Evaluation of erythrocytic total and oligomeric α-syn concentrations and the receiver operating characteristic curves for erythrocytic α-syn species and an integrative model to differentiate PD from HC. (A) Assessment of erythrocytic total α-syn levels. ***p < 0.001. (B) Assessment of erythrocytic oligomeric α-syn levels. ***p < 0.001. (C) Receiver operating characteristic curve for erythrocytic total α-syn adjusted for age and sex to differentiate PD from HC. (D) Receiver operating characteristic curve for erythrocytic oligomeric α-syn adjusted for age and sex to differentiate PD from HC. (E) Receiver operating characteristic curve for the multivariable model to differentiate PD from HC. The multivariable model includes erythrocytic total α-syn and erythrocytic oligomeric α-syn levels, controlling for age and sex. Univariate general linear model with the controlling of age and sex was used for two factor comparisons. HC, healthy control; PD, Parkinson’s disease; AUC, area under curve; α-syn, α-synuclein.

FIGURE 2

Correlation analysis of erythrocytic total and oligomeric α-syn concentrations with clinical characteristics in PD. (A) Erythrocytic total α-syn concentrations adjusted by age and sex were significantly correlated with HAMA scales (p = 0.016, r = –0.292) in PD patients. (C) No significant correlations between erythrocytic total α-syn concentrations and HAMD scales (p = 0.140, r = –0.182) were observed in PD patients. (B,D) Erythrocytic oligomeric α-syn concentrations were not correlated with HAMD scales (p = 0.291, r = 0.131) and HAMA scales (p = 0.649, r = 0.057) in PD patients. (E) Significant correlations between MDS-UPDRS III scores and erythrocytic total α-syn levels (p < 0.001, r = 0.455) were found in PD patients. (F) No correlations were found between MDS-UPDRS III scores and erythrocytic oligomeric α-syn levels (p = 0.368, r = 0.107). Dash lines represent 95% confidence intervals. Partial correlation analysis with the controlling of age and sex was used to assess the correlations. α-syn, α-synuclein; HAMA, Hamilton Anxiety Rating Scale; HAMD, 17-item Hamilton Depression Rating Scale; MDS-UPDRS III, Movement Disorder Society sponsored Unified Parkinson’s Disease Rating Scale Part-III; RBC, red blood cell.