title: Association between DNA Methylation of the BDNF Promoter Region and Clinical Presentation in Alzheimer's Disease.
abstract: OBJECTIVE
  In the present study, we examined whether DNA methylation of the brain-derived neurotrophic factor (BDNF) promoter is associated with the manifestation and clinical presentation of Alzheimer's disease (AD).
  
  
  METHODS
  Of 20 patients with AD and 20 age-matched normal controls (NCs), the DNA methylation of the BDNF promoter (measured using peripheral blood samples) was completely analyzed in 12 patients with AD and 6 NCs. The resulting methylation levels were compared statistically. Next, we investigated the correlation between the DNA methylation levels and the clinical presentation of AD.
  
  
  RESULTS
  The total methylation ratio (in %) of the 20 CpG sites was significantly higher in the AD patients (5.08 ± 5.52%) than in the NCs (2.09 ± 0.81%; p < 0.05). Of the 20 CpG sites, the methylation level at the CpG4 site was significantly higher in the AD subjects than in the NCs (p < 0.05). Moreover, the methylation level was significantly and negatively correlated with some neuropsychological test subscores (registration, recall, and prehension behavior scores; p < 0.05).
  
  
  CONCLUSIONS
  These results suggest that the DNA methylation of the BDNF promoter may significantly influence the manifestation of AD and might be associated with its neurocognitive presentation.
authors: Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan ; Division of Molecular Genetics, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors: Tomoyuki
authors: T
authors: Nagata
authors: Department of Virology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Nobuyuki
authors: N
authors: Kobayashi
authors: Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan.
authors: Jumpei
authors: J
authors: Ishii
authors: Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan.
authors: Shunichiro
authors: S
authors: Shinagawa
authors: Division of Molecular Genetics, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors: Ritsuko
authors: R
authors: Nakayama
authors: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors: Nobuto
authors: N
authors: Shibata
authors: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors: Bolati
authors: B
authors: Kuerban
authors: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors: Tohru
authors: T
authors: Ohnuma
authors: Department of Virology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Kazuhiro
authors: K
authors: Kondo
authors: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors: Heii
authors: H
authors: Arai
authors: Division of Molecular Genetics, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors: Hisashi
authors: H
authors: Yamada
authors: Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan.
authors: Kazuhiko
authors: K
authors: Nakayama
keywords: Alzheimer's disease; BDNF; Brain-derived neurotrophic factor; DNA methylation; Epigenetics; Neurotrophic factors