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

Lan Chang,Huadan Ye,Honglei Yin,Yuzheng Zhang,Huihui Ji,Qingxiao Hong,Xuting Xu,Shiwei Duan,Zhongming Chen,Yunliang Wang,Xiaonan Zhang,Danjie Jiang,Congcong Mao,Yu Liu,Qinwen Wang,Dongjun Dai,Dongsheng Zhou,Xiaohui Zhou,Jinfeng Li,Ying Liu ,Ren‐Xi Zhuo

doi:10.1371/journal.pone.0110773

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.

Highlights

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory disorder and cognitive dysfunction [1]
Our results showed that there was no significant interaction between AD drugs and Brain derived neurotrophic factor (BDNF) methylation or individual CpG sites (p.0.05, Figure S1 and Table S2)
Lower SORL1 promoter methylation was found in the brain and blood of AD patients [48]

Summary

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory disorder and cognitive dysfunction [1]. The prevalence of AD was 26.6 million in 2006, and the number is expected to quadruple in 2050, causing a huge burden on both family and society [2]. AD is a complex disease affected by both environmental and genetic factors [3]. Twin studies showed that approximately 80% of cases resulted from inheritance [4]. A handful of genetic markers have been identified [5], the pathogenesis of AD remains unclear. Environmental factors were shown to be related to AD [6]

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Conclusion