Multiregional analysis of global 5-methylcytosine and 5-hydroxymethylcytosine throughout the progression of Alzheimer's disease.
Multiregional analysis of global 5-methylcytosine and 5-hydroxymethylcytosine throughout the progression of Alzheimer's disease.
复制标题
在整个阿尔茨海默氏病的过程中，全球5-甲基胞嘧啶和5-羟基环霉素的多区域分析。
DOI：
10.1111/jnc.13912
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发表时间：
2017-02
影响因子：
4.7
通讯作者：
Lovell MA
中科院分区：
文献类型：
--
作者：
Ellison EM;Abner EL;Lovell MA
已知胞嘧啶的表观遗传修饰可以改变转录状态并解除癌症、胚胎发育以及最近的神经退行性疾病中基因表达的调节。为了检验胞嘧啶修饰的整体水平在阿尔茨海默病的整个进展过程中发生变化的假设，使用气相色谱/质谱 (GC/MS) 和稳定标记的胞嘧啶、5-mC 和 5-hmC 内标对 5-甲基胞嘧啶 (5-mC) 和 5-羟甲基胞嘧啶 (5-hmC) 进行定量。对认知正常对照 (NC) 受试者和患有轻度认知障碍 (MCI)、临床前阿尔茨海默病 (PCAD)、迟发性阿尔茨海默病 (LOAD)、额颞叶变性 (FTLD) 和痴呆受试者的四个脑区（小脑、顶下叶、颞上回和颞中回以及海马/海马旁回）组织样本中提取的 DNA 中的胞嘧啶修饰进行定量路易体 (DLB)。对数据的重复测量分析显示，阿尔茨海默病（PCAD 和 MCI）早期阶段以及 FTLD 和 DLB 受试者大脑多个区域的 5-mC 和 5-hmC 发生显着变化。这些数据表明基因表观遗传调控的改变可能在 AD 以及其他类型的神经退行性疾病的进展中发挥早期作用。胞嘧啶修饰可以改变转录状态，并可能在阿尔茨海默病 (AD) 中发挥作用。使用气相色谱质谱法对正常衰老、临床前 AD (PCAD)、轻度认知障碍 (MCI)、晚发 AD (LOAD)、额颞叶变性 (FTLD) 和路易体痴呆 (DLB) 受试者的 AD 受影响大脑区域的 DNA 进行分析。在 AD 早期阶段观察到 5-甲基胞嘧啶 (5-mC) 和 5-羟甲基胞嘧啶 (5-hmC) 的变化，表明表观遗传修饰在 AD 进展中可能发挥作用。
Epigenetic modifications to cytosine are known to alter transcriptional states and deregulate gene expression in cancer, embryonic development, and most recently in neurodegeneration. To test the hypothesis that global levels of cytosine modification are altered throughout the progression of Alzheimer’s disease, 5-methylcytosine (5-mC) and 5-hydroxmethylcytosine (5-hmC) were quantified using gas chromatography/mass spectrometry (GC/MS) and stable labeled internal standards of cytosine, 5-mC, and 5-hmC. Cytosine modifications were quantified in DNA extracted from tissue specimens of four brain regions (cerebellum, inferior parietal lobe, superior and middle temporal gyrus, and hippocampus/parahippocampal gyrus) of cognitively normal control (NC) subjects and subjects with mild cognitive impairment (MCI), preclinical Alzheimer’s disease (PCAD), late onset Alzheimer’s disease (LOAD), frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies (DLB). Repeated measures analyses of the data show significant alterations in 5-mC and 5-hmC in early stages of Alzheimer’s disease (PCAD and MCI), as well as FTLD and DLB subjects, across multiple regions of the brain. These data suggest alterations in epigenetic regulation of genes may play an early role in the progression of AD as well as other types of neurodegeneration. Cytosine modifications can alter transcriptional states and may play a role in Alzheimer’s disease (AD). DNA from AD affected brain regions was analyzed using gas chromatography mass spectrometry for normal aging, preclinical AD (PCAD), mild cognitive impairment (MCI), late onset AD (LOAD), frontotemporal lobar degeneration (FTLD), and dementia with Lewy bodies (DLB) subjects. Alterations in 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) were seen in early stages of AD, indicating a possible role of epigenetic modification in AD progression.