title: DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy in Alzheimer's disease and amnesic mild cognitive impairment patients.
abstract: Several studies have noted an effect of DNA methylation on the pathogenesis of Alzheimer's disease (AD). We have already reported that DNA methylation levels in the NCAPH2/LMF2 promoter region can be a useful biomarker for the diagnosis of AD and amnesic mild cognitive impairment (aMCI). However, there is still uncertainty about the mechanism by which NCAPH2/LMF2 methylation affects the pathogenesis of AD and aMCI. In this study, we investigated relationships between NCAPH2/LMF2 methylation and other factors. AD (n=30) and aMCI (n=28) subjects were included in this study. NCAPH2/LMF2 methylation levels were measured by pyrosequencing. Correlations between methylation levels and other factors including age at onset, sex, duration of disease, education, mini-mental state examination (MMSE) and frontal assessment battery (FAB) scores, APOE genotype, degree of hippocampal atrophy, and total brain atrophy were measured. Degrees of hippocampal atrophy and total brain atrophy were measured by VSRAD (Voxel-Based Specific Regional Analysis System for Alzheimer's Disease). Regression analysis revealed that only hippocampal atrophy according to VSRAD is a significant dependent variable correlated with NCAPH2/LMF2 methylation levels. Our results suggest that DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy through apoptosis.
authors.affiliation: Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: shinagawa@jikei.ac.jp.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Shinagawa
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; 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 Psychiatry, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kusaka
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 Virology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D000647:Amnesia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001284:Atrophy / Q000235:genetics / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000150:complications / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012697:Serine Endopeptidases
chemical_list: D015415:Biomarkers; D018797:Cell Cycle Proteins; C572282:Ncaph2 protein, mouse; D009687:Nuclear Proteins; C472564:PRSS27 protein, human; D012697:Serine Endopeptidases
keywords: Alzheimer's disease: mild cognitive impairment patients; DNA methylation; Hippocampal atrophy