title: Usefulness of DNA Methylation Levels in COASY and SPINT1 Gene Promoter Regions as Biomarkers in Diagnosis of Alzheimer's Disease and Amnestic Mild Cognitive Impairment.
abstract: In order to conduct early therapeutic interventions for Alzheimer's disease (AD), convenient, early diagnosis markers are required. We previously reported that changes in DNA methylation levels were associated with amnestic mild cognitive impairment (aMCI) and AD. As the results suggested changes in DNA methylation levels in the COASY and SPINT1 gene promoter regions, in the present study we examined DNA methylation in these regions in normal controls (NCs, n = 30), aMCI subjects (n = 28) and AD subjects (n = 30) using methylation-sensitive high resolution melting (MS-HRM) analysis. The results indicated that DNA methylation in the two regions was significantly increased in AD and aMCI as compared to NCs (P < 0.0001, P < 0.0001, ANOVA). Further analysis suggested that DNA methylation in the COASY gene promoter region in particular could be a high sensitivity, high specificity diagnosis biomarker (COASY: sensitivity 96.6%, specificity 96.7%; SPINT1: sensitivity 63.8%, specificity 83.3%). DNA methylation in the COASY promoter region was associated with CDR Scale Sum of Boxes (CDR-SB), an indicator of dementia severity. In the SPINT1 promoter region, DNA methylation was negatively associated with age in NCs and elevated in aMCI and AD subjects positive for antibodies to Herpes simplex virus type 1 (HSV-1). These findings suggested that changes in DNA methylation in the COASY and SPINT1 promoter regions are influenced by various factors. In conclusion, DNA methylation levels in the COASY and SPINT1 promoter regions were considered to potentially be a convenient and useful biomarker for diagnosis of AD and aMCI.
authors.affiliation: Department of Virology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Nobuyuki
authors.identifier: http://orcid.org/0000-0001-8627-515X
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Shinagawa
authors.affiliation: Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan.|Division of Molecular Genetics, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nagata
authors.affiliation: Department of Virology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Nobuto
authors.initials: N
authors.lastname: Shibata
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohnuma
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kasanuki
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
authors.affiliation: Division of Molecular Genetics, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Virology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kondo
mesh_terms: D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism*; D000914:Antibodies, Viral / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D018259:Herpesvirus 1, Human; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D053491:Proteinase Inhibitory Proteins, Secretory / Q000378:metabolism*; D014166:Transferases / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D053491:Proteinase Inhibitory Proteins, Secretory; C109149:SPINT1 protein, human; D014166:Transferases; C509687:COASY protein, human