title: Elevated mRNA Expression and Low Methylation of SNCA in Japanese Alzheimer's Disease Subjects.
abstract: Despite the continuing debate about the amyloid hypothesis in Alzheimer's disease (AD), the precise pathogenesis is still unclear. Mixed pathology is common and multiple different protein aggregates are seen in human postmortem brains. Aggregates consisting of the alpha-synuclein protein encoded by the Synuclein Alpha gene (SCNA) are common in both dementia with Lewy bodies and AD. We examined SNCA mRNA expression and methylation rates of the CpG island at intron 1 of SNCA in peripheral leukocytes in 50 AD and age- and sex-matched control subjects to verify whether alpha-synuclein pathology affects the AD pathogenesis. SNCA mRNA expression in AD subjects was significantly higher than that in control subjects (1.62±0.73 versus 0.98±0.50, p < 0.001). We found significant differences between AD and control subjects at seven CpG sites (average rate; 8.8±2.7 versus 9.5±2.5, respectively: p = 0.027). The methylation rates tended to be lower in AD subjects at all CpG sites. We conclude that mRNA expression and methylation of SNCA intron 1 are altered in AD, which may be caused by Lewy body pathology in AD.
authors: Yuta
authors: Y
authors: Yoshino
authors: Takaaki
authors: T
authors: Mori
authors: Taku
authors: T
authors: Yoshida
authors: Kiyohiro
authors: K
authors: Yamazaki
authors: Yuki
authors: Y
authors: Ozaki
authors: Tomoko
authors: T
authors: Sao
authors: Yu
authors: Y
authors: Funahashi
authors: Jun-Ichi
authors: JI
authors: Iga
authors: Shu-Ichi
authors: SI
authors: Ueno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008745:Methylation; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C497604:SNCA protein, human; D051844:alpha-Synuclein
keywords: Alpha-synuclein; Alzheimer’s disease; Lewy bodies; SNCA; methylation