School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
Int J Mol Sci. 2024 May 29;25(11):5970. doi: 10.3390/ijms25115970.
Epigenetic modifications have been implicated in a number of complex diseases as well as being a hallmark of organismal aging. Several reports have indicated an involvement of these changes in Alzheimer's disease (AD) risk and progression, most likely contributing to the dysregulation of AD-related gene expression measured by DNA methylation studies. Given that DNA methylation is tissue-specific and that AD is a brain disorder, the limitation of these studies is the ability to identify clinically useful biomarkers in a proxy tissue, reflective of the tissue of interest, that would be less invasive, more cost-effective, and easily obtainable. The age-related DNA methylation changes have also been used to develop different generations of epigenetic clocks devoted to measuring the aging in different tissues that sometimes suggests an age acceleration in AD patients. This review critically discusses epigenetic changes and aging measures as potential biomarkers for AD detection, prognosis, and progression. Given that epigenetic alterations are chemically reversible, treatments aiming at reversing these modifications will be also discussed as promising therapeutic strategies for AD.
表观遗传修饰与许多复杂疾病有关，也是生物体衰老的标志。有几项报告表明，这些变化与阿尔茨海默病（AD）的风险和进展有关，它们很可能导致 AD 相关基因表达的失调，这可以通过 DNA 甲基化研究来衡量。鉴于 DNA 甲基化具有组织特异性，并且 AD 是一种脑部疾病，这些研究的局限性在于能够在一个替代组织中识别出具有临床意义的生物标志物，该标志物反映了感兴趣的组织，其侵入性更小、更具成本效益，并且易于获得。与年龄相关的 DNA 甲基化变化也被用于开发不同代的表观遗传时钟，用于测量不同组织中的衰老程度，这些时钟有时表明 AD 患者的衰老加速。这篇综述批判性地讨论了表观遗传变化和衰老测量作为 AD 检测、预后和进展的潜在生物标志物。鉴于表观遗传改变是化学可逆的，旨在逆转这些修饰的治疗方法也将被讨论为 AD 的有前途的治疗策略。
