Objective: To investigate serum α-synuclein levels in Huntington’s disease (HD) patients.

Background: HD is a heredodegenerative disease caused by mutations in HTT coding for huntingtin (Htt). A cross-talk between Htt aggregation and α-synuclein has been reported, even though the mechanism underlying such interaction is still obscure. Elevated serum α-synuclein has been demonstrated in other neurodegenerative diseases such as Parkinson’s disease, in contrast to the declining levels of serum α-synuclein observed with normal ageing.

Methods: In total, 32 consecutive symptomatic patients with molecularly confirmed HD, 4 presymptomatic subjects positive for the HD expansion and 14 control subjects were recruited from the Neurogenetics outpatient clinic. Peripheral blood was collected during clinic visits, allowed to coagulate and centrifuged for serum collection. Serum α-synuclein was measured using our in house ELISA. For statistical analysis symptomatic and presymptomatic HD patients were grouped together. Chi-square tests, ANOVA and ANCOVA were used as appropriate to investigate differences between groups. Correlations between groups were investigated using Pearson’s method. All statistical analysis was performed on SPSS v.20.

Results: HD and control groups were well matched for sex, but not for age (HD patients on average 10 years older than controls) or medication (69% of HD group on symptomatic treatment vs. 0% of controls). Serum α-synuclein levels were significantly higher in HD patients vs. controls (p=0.004). To control for the age difference between HD and controls, we used ANCOVA with age as covariate, which did not affect the significance of the result (p=0.010). Serum α-synuclein levels did not differ significantly between male and female HD patients (2.45 ± 0.94 vs 2.43 ± 1.46 ng/ml; p=0.972, ANOVA). Serum α-synuclein levels did not differ significantly between HD patients receiving medication and HD patients not receiving medication (2.33 ± 1.19 vs 2.56 ± 1.53 ng/ml; p=0.639, ANOVA). Within the HD group, serum α-synuclein levels did not correlate significantly with CAG2, UHDRS motor score, age or disease duration.

Conclusions: Our results provide evidence for elevated serum α-synuclein levels in HD patients. Insights on α-synuclein levels may shed further light on the mechanism of pathological Htt aggregation and contribute to the identification of robust biomarkers of disease progression in HD. Further investigation in larger populations is needed to support our findings.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/elevated-serum-%ce%b1-synuclein-levels-in-huntingtons-disease-patients/