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

AimIt 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 -synuclein protein is a major component of Lewy bodies, and accumulation of -synuclein aggregates causes synaptic dysfunction in DLB. Epigenetic changes at the synuclein alpha (SNCA) gene may be involved in DLB pathogenesis. MethodsWe 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=78.87.7years) with healthy controls (n=20; eight men, 12 women; age=77.0 6.9years). ResultsThe 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. ConclusionOur findings indicated that lower methylation rates may be a biomarker for DLB.