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.
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.
Authors: Peter D Fransquet; Paul Lacaze; Richard Saffery; John McNeil; Robyn Woods; Joanne Ryan Journal: Alzheimers Dement Date: 2017-11-08 Impact factor: 21.566
Authors: Peter D Fransquet; Paul Lacaze; Richard Saffery; James Phung; Emily Parker; Raj C Shah; Anne Murray; Robyn L Woods; Joanne Ryan Journal: Epigenomics Date: 2020-12-10 Impact factor: 4.778
Authors: Jessica Tulloch; Lesley Leong; Sunny Chen; C Dirk Keene; Steven P Millard; Andrew Shutes-David; Oscar L Lopez; Julia Kofler; Jeffrey A Kaye; Randy Woltjer; Peter T Nelson; Janna H Neltner; Gregory A Jicha; Douglas Galasko; Eliezer Masliah; James B Leverenz; Chang-En Yu; Debby Tsuang Journal: Alzheimers Dement Date: 2018-03-12 Impact factor: 21.566
Authors: Ernesto Miranda-Morales; Karin Meier; Ada Sandoval-Carrillo; José Salas-Pacheco; Paola Vázquez-Cárdenas; Oscar Arias-Carrión Journal: Front Mol Neurosci Date: 2017-07-18 Impact factor: 5.639