N6-甲基腺嘌呤修饰的DNA在阿尔茨海默病患者中减少。
N6-methyladenine-modified DNA was decreased in Alzheimer's disease patients.
作者信息
Lv Shuang, Zhou Xiao, Li Yi-Ming, Yang Tao, Zhang Shu-Juan, Wang Yu, Jia Shu-Hong, Peng Dan-Tao
机构信息
Department of Neurology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China.
Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China.
出版信息
World J Clin Cases. 2022 Jan 14;10(2):448-457. doi: 10.12998/wjcc.v10.i2.448.
BACKGROUND
In recent years, the prevalence of Alzheimer's disease (AD) has increased, which places a great burden on society and families and creates considerable challenges for medical services. N6-methyladenine (m6A) deoxyribonucleic acid (DNA) adenine methylation is a novel biomarker and is abundant in the brain, but less common in AD. We support to analyze the relationship between DNA m6A and cognition in patients with AD and normal controls (NCs) in China.
AIM
To analyze the relationship between the novel m6A DNA and cognition in patients with AD and NCs in China.
METHODS
A total of 179 AD patients (mean age 71.60 ± 9.89 years; males: 91; females: 88) and 147 NCs (mean age 69.59 ± 11.22 years; males: 77; females: 70) who were age- and sex-matched were included in our study. All subjects underwent neuropsychological scale assessment and magnetic resonance imaging examination. Apolipoprotein E (APOE) genotypes were measured through agarose gel electrophoresis. Global m6A levels were evaluated by a MethylFlash m6A DNA Methylation ELISA Kit (colorimetric). Global m6A levels in total DNA from ten AD patients with 18F-AV-45 (florbetapir) positron emission tomography (PET) positivity and ten NCs with PET negativity were analyzed by dot blotting to determine the results.
RESULTS
Our ELISA results showed that the global m6A DNA levels in peripheral blood were different between patients with AD and NCs ( = 0.002; < 0.05). And ten AD patients who were PET positive and ten NCs who were PET negative also showed the same results through dot blotting. There were significant differences between the two groups, which indicated that the leukocyte m6A DNA levels were different ( = 0.005; < 0.05). The m6A level was approximately 8.33% lower in AD patients than in NCs (mean 0.011 ± 0.006 0.012 ± 0.005). A significant correlation was found between the Montreal Cognitive Assessment score and the peripheral blood m6A level in the tested population ( = 0.143, = 0.01; < 0.05). However, no relationship was found with APOE ε4 ( = 0.633, > 0.05). Further studies should be performed to validate these findings.
CONCLUSION
Our results show that reduced global m6A DNA methylation levels are significantly lower in AD patients than in NCs by approximately 8.33% in China.
背景
近年来，阿尔茨海默病（AD）的患病率有所上升，这给社会和家庭带来了沉重负担，也给医疗服务带来了巨大挑战。N6-甲基腺嘌呤（m6A）脱氧核糖核酸（DNA）腺嘌呤甲基化是一种新型生物标志物，在大脑中含量丰富，但在AD中较少见。我们支持分析中国AD患者和正常对照（NCs）中DNA m6A与认知之间的关系。
目的
分析中国AD患者和NCs中新型m6A DNA与认知之间的关系。
方法
本研究纳入了179例AD患者（平均年龄71.60±9.89岁；男性91例；女性88例）和147例年龄和性别匹配的NCs（平均年龄69.59±11.22岁；男性77例；女性70例）。所有受试者均接受了神经心理量表评估和磁共振成像检查。通过琼脂糖凝胶电泳检测载脂蛋白E（APOE）基因型。采用MethylFlash m6A DNA甲基化ELISA试剂盒（比色法）评估总体m6A水平。通过斑点印迹法分析10例18F-AV-45（氟代贝他吡）正电子发射断层扫描（PET）阳性的AD患者和10例PET阴性的NCs的总DNA中的总体m6A水平，以确定结果。
结果
我们的ELISA结果显示，AD患者和NCs外周血中的总体m6A DNA水平存在差异（ = 0.002；<0.05）。10例PET阳性的AD患者和10例PET阴性的NCs通过斑点印迹法也显示出相同的结果。两组之间存在显著差异，这表明白细胞m6A DNA水平不同（ = 0.005；<0.05）。AD患者的m6A水平比NCs低约8.33%（平均值0.011±0.006对0.012±0.005）。在受试人群中，蒙特利尔认知评估得分与外周血m6A水平之间存在显著相关性（ = 0.143， = 0.01；<0.05）。然而，未发现与APOE ε4存在相关性（ = 0.633，>0.05）。应进行进一步研究以验证这些发现。
结论
我们的结果表明，在中国，AD患者的总体m6A DNA甲基化水平降低，比NCs显著低约8.33%。
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