A growing number of epigenome-wide association studies have demonstrated a role for DNA methylation in the brain in Alzheimer's disease. With the aim of exploring peripheral biomarker potential, we have examined DNA methylation patterns in whole blood collected from 284 individuals in the AddNeuroMed study, which included 89 nondemented controls, 86 patients with Alzheimer's disease, and 109 individuals with mild cognitive impairment, including 38 individuals who progressed to Alzheimer's disease within 1 year. We identified significant differentially methylated regions, including 12 adjacent hypermethylated probes in the HOXB6 gene in Alzheimer's disease, which we validated using pyrosequencing. Using weighted gene correlation network analysis, we identified comethylated modules of genes that were associated with key variables such as APOE genotype and diagnosis. In summary, this study represents the first large-scale epigenome-wide association study of Alzheimer's disease and mild cognitive impairment using blood. We highlight the differences in various loci and pathways in early disease, suggesting that these patterns relate to cognitive decline at an early stage.

中文翻译：

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一项对阿尔茨海默病血液的表观基因组关联研究强调了 HOXB6 基因中强大的 DNA 高甲基化

越来越多的表观基因组关联研究证明了阿尔茨海默病大脑中 DNA 甲基化的作用。为了探索外周生物标志物的潜力，我们检查了 AddNeuroMed 研究中从 284 名个体采集的全血中的 DNA 甲基化模式，其中包括 89 名非痴呆对照、86 名阿尔茨海默病患者和 109 名轻度认知障碍患者，其中包括 38 名个体谁在 1 年内发展为阿尔茨海默病。我们确定了显着的差异甲基化区域，包括阿尔茨海默病中 HOXB6 基因中的 12 个相邻的高甲基化探针，我们使用焦磷酸测序对其进行了验证。使用加权基因相关网络分析，我们确定了与 APOE 基因型和诊断等关键变量相关的基因共甲基化模块。总之，这项研究代表了第一个使用血液的阿尔茨海默病和轻度认知障碍的大规模表观基因组关联研究。我们强调了早期疾病中各种基因座和途径的差异，表明这些模式与早期认知衰退有关。