DNA methylation changes at SNCA intron 1 in patients with dementia with Lewy bodies

Abstract

Aim: It is difficult to diagnose dementia with Lewy bodies (DLB) because it exhibits clinical and neuropathological overlap with both Alzheimer's disease and Parkinson's disease. The α-synuclein protein is a major component of Lewy bodies, and accumulation of α-synuclein aggregates causes synaptic dysfunction in DLB. Epigenetic changes at the synuclein alpha (SNCA) gene may be involved in DLB pathogenesis. Methods: We examined DNA methylation rates at 10 CpG sites located in intron 1 of SNCA and SNCA mRNA expression in peripheral leukocytes to compare DLB patients (n = 20; nine men, 11 women; age = 78.8 ± 7.7 years) with healthy controls (n = 20; eight men, 12 women; age = 77.0 ± 6.9 years). Results: The methylation rate at CpG 4 (P = 0.002) and the overall mean methylation rate at these sites (P < 0.001) were significantly lower in DLB patients than in healthy controls after Bonferroni correction. Although SNCA126, a partial form of SNCA mRNA expression, was significantly increased in DLB (P = 0.017), there was no significant difference in total SNCA mRNA expression between DLB patients and healthy controls (P = 0.165). No correlation was observed between SCNA mRNA expression levels and blood DNA methylation rates in either DLB or healthy controls. Conclusion: Our findings indicated that lower methylation rates may be a biomarker for DLB.