Association between DNA Methylation of the BDNF Promoter Region and Clinical Presentation in Alzheimer's Disease.
Association between DNA Methylation of the BDNF Promoter Region and Clinical Presentation in Alzheimer's Disease.
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DOI：
10.1159/000375367
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发表时间：
2015-01
影响因子：
2.3
通讯作者：
Nakayama K
中科院分区：
文献类型：
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作者：
Nagata T;Kobayashi N;Ishii J;Shinagawa S;Nakayama R;Shibata N;Kuerban B;Ohnuma T;Kondo K;Arai H;Yamada H;Nakayama K
在本研究中，我们研究了脑源性神经营养因子（BDNF）启动子的DNA甲基化是否与阿尔茨海默病（AD）的表现和临床表现相关。在20例AD患者和20例年龄匹配的正常对照（NC）中，对12例AD患者和6例NC患者的BDNF启动子DNA甲基化（使用外周血样本测量）进行了全面分析。统计学上比较所得甲基化水平。接下来，我们研究了DNA甲基化水平与AD临床表现之间的相关性。AD患者20个CpG位点的总甲基化率（%）（5.08 ± 5.52%）显著高于NC（2.09 ± 0.81%; p < 0.05）。在20个CpG位点中，AD受试者中CpG 4位点的甲基化水平显著高于NC（p < 0.05）。此外，甲基化水平与一些神经心理学测试子评分（注册，回忆和回避行为评分; p < 0.05）呈显著负相关。这些结果提示BDNF基因启动子区甲基化可能对AD的临床表现有显著影响，并可能与AD的神经认知表现有关。
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). 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. 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). 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.