title: Development of Biomarkers Based on DNA Methylation in the NCAPH2/LMF2 Promoter Region for Diagnosis of Alzheimer's Disease and Amnesic Mild Cognitive Impairment.
abstract: From the standpoint of early interventions for dementia, a convenient method of diagnosis using biomarkers is required for Alzheimer's disease (AD) in the early stage as well as amnesic mild cognitive impairment (aMCI). Focusing on differences in DNA methylation due to AD and aMCI, in the present study, we first conducted genome-wide screening, measuring blood DNA methylation levels by the Illumina Infinium HD Methylation Assay in 3 small age-and gender-matched groups consisting of 4 subjects each: normal controls (NC), aMCI and AD. The genome-wide analysis produced 11 DNA methylation loci that distinguished the 3 groups. For confirmation, we increased group sizes and examined samples by pyrosequencing which revealed that DNA methylation in the NCAPH2/LMF2 promoter region was significantly decreased in the AD (n = 30) and aMCI (n = 28) groups as compared to the NC group (n = 30) (P < 0.0001, ANCOVA). No association was found between methylation levels and APOE genotype. NCAPH2/LMF2 methylation levels 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.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: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics; D000647:Amnesia / Q000175:diagnosis* / Q000235:genetics; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D056426:Genetic Loci; D005819:Genetic Markers; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D005819:Genetic Markers