Development of Biomarkers Based on DNA Methylation in the NCAPH2/LMF2 Promoter Region for Diagnosis of Alzheimer's Disease and Amnesic Mild Cognitive Impairment

PLoS One. 2016 Jan 7;11(1):e0146449. doi: 10.1371/journal.pone.0146449. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics
  • Amnesia / diagnosis*
  • Amnesia / genetics
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / genetics
  • CpG Islands
  • DNA Methylation
  • Female
  • Genetic Loci
  • Genetic Markers
  • Humans
  • Male
  • Promoter Regions, Genetic
  • Sequence Analysis, DNA

Substances

  • Genetic Markers

Grants and funding

The present work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI (grant number 25893251, TN, https://www.jsps.go.jp/j-grantsinaid/), the Jikei University Research Fund (SS, http://www.jikei.ac.jp), The Ministry of Education, Culture, Sports, Science and Technology (MEXT)-Supported Program for the Strategic Research Foundation at Private Universities (grant number S1201032, co-researcher: K. Kondo, http://www.mext.go.jp/a_menu/koutou/shinkou/07021403/002/002/1218299.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.