Elevation of peripheral BDNF promoter methylation links to the risk of Alzheimer's disease

PLoS One. 2014 Nov 3;9(11):e110773. doi: 10.1371/journal.pone.0110773. eCollection 2014.

Abstract

Brain derived neurotrophic factor (BDNF) has been known to play an important role in various mental disorders or diseases such as Alzheimer's disease (AD). The aim of our study was to assess whether BDNF promoter methylation in peripheral blood was able to predict the risk of AD. A total of 44 AD patients and 62 age- and gender-matched controls were recruited in the current case-control study. Using the bisulphite pyrosequencing technology, we evaluated four CpG sites in the promoter of the BDNF. Our results showed that BDNF methylation was significantly higher in AD cases than in the controls (CpG1: p = 10.021; CpG2: p = 0.002; CpG3: p = 0.007; CpG4: p = 0.005; average methylation: p = 0.004). In addition, BDNF promoter methylation was shown to be significantly correlated with the levels of alkaline phosphatase (ALP), glucose, Lp(a), ApoE and ApoA in males (ALP: r = -0.308, p = 0.042; glucose: r = -0.383, p = 0.010; Lp(a): r = 0.333, p = 0.027; ApoE: r = -0.345, p = 0.032;), ApoA levels in females (r = 0.362, p = 0.033), and C Reactive Protein (CRP) levels in both genders (males: r = -0.373, p = 0.016; females: r = -0.399, p = 0.021). Our work suggested that peripheral BDNF promoter methylation might be a diagnostic marker of AD risk, although its underlying function remains to be elaborated in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Case-Control Studies
  • Comorbidity
  • CpG Islands
  • DNA Methylation*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Promoter Regions, Genetic*
  • Risk
  • Risk Factors

Substances

  • Brain-Derived Neurotrophic Factor

Grants and funding

The research was supported by grants from: National Natural Science Foundation of China (31100919 and 81371469), 973 Program from the Ministry of Science and Technology of China (2013CB835100), Natural Science Foundation of Zhejiang Province (LR13H020003), Disciplinary Project of Ningbo University (B01350104900), C. Wong Magna Fund in Ningbo University, and Ningbo Social Development Research Projects (2012C50032). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.