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


CONCLUSIONS
Our findings indicated that lower methylation rates may be a biomarker for DLB.
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, Japan.
Yu
Y
Funahashi
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, Japan.
Yuta
Y
Yoshino
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, Japan.
Kiyohiro
K
Yamazaki
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, Japan.
Yoko
Y
Mori
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, Japan.
Takaaki
T
Mori
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, Japan.
Yuki
Y
Ozaki
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, Japan.
Tomoko
T
Sao
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, Japan.
Shinichiro
S
Ochi
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, Japan.
Jun-Ichi
http://orcid.org/0000-0003-4409-3096
JI
Iga
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, Japan.
Shu-Ichi
SI
Ueno
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation / Q000502:physiology*; D005260:Female; D006801:Humans; D007438:Introns; D020961:Lewy Body Disease / Q000097:blood / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
D015415:Biomarkers; D012333:RNA, Messenger; C497604:SNCA protein, human; D051844:alpha-Synuclein

SNCA gene; dementia with Lewy bodies; gene expression; methylation; pyrosequencer