In late 2014, the first epigenome‐wide association studies of DNA modifications in Alzheimer’s disease brain samples were published. Over the last 5 years, further studies have been reported in the field and have highlighted consistent and robust alterations in DNA modifications in AD cortex. However, there are some caveats associated with the majority of studies undertaken to date; for example, they are predominantly restricted to profiling a limited number of loci, are principally focused on DNA methylation, are performed on bulk tissue at the end stage of disease and are restricted to nominating associations rather than demonstrating causal relationships. Consequently, the downstream interpretation of these studies is limited. Owing to recent advances in state‐of‐the‐art cell profiling techniques, long‐read genomic technologies and genetic engineering methodologies, identifying cell‐type‐specific causal epigenetic changes is becoming feasible. This review seeks to provide an overview of the last 5 years of epigenomic studies of DNA modifications in Alzheimer’s disease brain samples and propose new avenues for future research.

中文翻译：

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阿尔茨海默病 DNA 修饰全表观基因组关联研究的五年更新：进展、实用性和前景。

2014 年底，首次发表了阿尔茨海默病大脑样本中 DNA 修饰的全表观基因组关联研究。在过去的 5 年中，该领域已经报道了进一步的研究，并强调了 AD 皮层 DNA 修饰的一致和稳健的改变。然而，迄今为止进行的大多数研究都存在一些警告；例如，它们主要限于分析有限数量的基因座，主要集中在 DNA 甲基化，在疾病末期对大量组织进行分析，并且仅限于指定关联而不是证明因果关系。因此，这些研究的下游解释是有限的。由于最先进的细胞分析技术的最新进展，长读长基因组技术和基因工程方法，识别细胞类型特异性因果表观遗传变化变得可行。本综述旨在概述过去 5 年对阿尔茨海默病大脑样本中 DNA 修饰的表观基因组研究，并为未来的研究提出新的途径。