Objective: We sought to investigate the relationship between SNCA Rep1 allele length and cognitive, motor and disability scores in PD, as well with plasma alpha-synuclein levels.

Background: Associations between the alpha-synuclein gene (SNCA) promoter region (Rep1) polymorphism (long- vs short-allele carriers) and Parkinson’s’ disease (PD) is well-established, with longer Rep1 allele carriers displaying increased risk of developing PD and greater motor decline in multiple studies than short allele carriers. Currently, the association of Rep1 allele length with PD cognition as well as with plasma alpha-synuclein levels remains unknown.

Methods: 129 subjects were included in this study (37 gender-matched controls and 92 PD patients). Subjects were grouped according to Rep1 allele length: 0/1 (short), 0/1-1/2 (medium) and 2/3 (long) in line with previous studies. All subjects underwent tests of global cognition (mini-mental state examination, MMSE), motor evaluation using the Unified Parkinson’s Disease Rating Scale (UPDRS) and disability scoring on the Hoehn & Yahr (H&Y) scale. Plasma alpha-synuclein was measured using Single Molecule Array (Simoa) technology.

Results: MMSE scores were significantly lower in PD than in controls (p<0.001, after adjusting for age and gender), with a non-significant trend towards lower MMSE scores in PD patients with longer vs shorter alleles (24.1 vs 25.4, p=0.40). While UPDRS motor scores did not vary according to Rep1 length, there was a higher frequency of short allele carriers (47%) than longer allele carriers (10%) in patients with milder disease (H&Y≤2; higher frequency of medium-length allele (55%) than shorter allele carriers (30%) in patients with moderate disease (H&Y≥2.5) and more longer allele carriers (15%) than that in milder disease group. Plasma alpha-synuclein levels were significantly higher in PD than controls (14976.4 vs 10845.0 pg/ml, p=0.002) but did not differ significantly according to Rep1 length.

Conclusions: Our findings suggest that the SNCA Rep1 promoter region may influence disease severity in PD, with a higher proportion of short Rep1 allele carriers amongst patients with milder disease. It is likely that more sensitive tests of cognition are required to confirm the association of Rep1 polymorphism and PD cognition in this study.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/investigating-the-influence-of-alpha-synuclein-promoter-rep1-polymorphism-on-cognition-disability-and-plasma-alpha-synuclein-levels-in-parkinsons-disease/