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

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

Lan Chang  1 , Yunliang Wang  2 , Huihui Ji  1 , Dongjun Dai  1 , Xuting Xu  1 , Danjie Jiang  1 , Qingxiao Hong  1 , Huadan Ye  1 , Xiaonan Zhang  1 , Xiaohui Zhou  3 , Yu Liu  1 , Jinfeng Li  2 , Zhongming Chen  4 , Ying Li  5 , Dongsheng Zhou  4 , Renjie Zhuo  1 , Yuzheng Zhang  2 , Honglei Yin  2 , Congcong Mao  1 , Shiwei Duan  1 , Qinwen Wang  1
Affiliations

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

Lan Chang et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Correlation among 4 CpGs in BDNF promoter.
F: Forward primer, R: Reverse primer, S: Sequencing primer.
Figure 2
Figure 2. Comparison of BDNF methylation levels between cases and controls.
Figure 3
Figure 3. Correlation analyses between the BDNF promoter methylation levels and the metabolic features of samples.
See this image and copyright information in PMC

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