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阿尔茨海默病的表观遗传学生物标志物:诊断和预后相关性。

Epigenetic biomarkers in Alzheimer's disease: Diagnostic and prognostic relevance.

机构信息

Amity School of Pharmaceutical Sciences, Amity University, Punjab 140306, India.

Marwadi University Research Center, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Marwadi University, Rajkot, Gujarat 360003, India.

出版信息

Ageing Res Rev. 2024 Dec;102:102556. doi: 10.1016/j.arr.2024.102556. Epub 2024 Oct 28.

Abstract

Alzheimer's disease (AD) is a leading cause of cognitive decline in the aging population, presenting a critical need for early diagnosis and effective prognostic tools. Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, have emerged as promising biomarkers for AD due to their roles in regulating gene expression and potential for reversibility. This review examines the current landscape of epigenetic biomarkers in AD, emphasizing their diagnostic and prognostic relevance. DNA methylation patterns in genes such as APP, PSEN1, and PSEN2 are highlighted for their strong associations with AD pathology. Alterations in DNA methylation at specific CpG sites have been consistently observed in AD patients, suggesting their utility in early detection. Histone modifications, such as acetylation and methylation, also play a crucial role in chromatin remodelling and gene expression regulation in AD. Dysregulated histone acetylation and methylation have been linked to AD progression, making these modifications valuable biomarkers. Non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), further contribute to the epigenetic regulation in AD. miRNAs can modulate gene expression post-transcriptionally and have been found in altered levels in AD, while lncRNAs can influence chromatin structure and gene expression. The presence of these non-coding RNAs in biofluids like blood and cerebrospinal fluid positions them as accessible and minimally invasive biomarkers. Technological advancements in detecting and quantifying epigenetic modifications have propelled the field forward. Techniques such as next-generation sequencing, bisulfite sequencing, and chromatin immunoprecipitation assays offer high sensitivity and specificity, enabling the detailed analysis of epigenetic changes in clinical samples. These tools are instrumental in translating epigenetic research into clinical practice. This review underscores the potential of epigenetic biomarkers to enhance the early diagnosis and prognosis of AD, paving the way for personalized therapeutic strategies and improved patient outcomes. The integration of these biomarkers into clinical workflows promises to revolutionize AD management, offering hope for better disease monitoring and intervention.

摘要

阿尔茨海默病(AD)是老龄化人口认知能力下降的主要原因,因此迫切需要早期诊断和有效的预后工具。表观遗传修饰,包括 DNA 甲基化、组蛋白修饰和非编码 RNA,由于它们在调节基因表达和潜在的可逆性方面的作用,已成为 AD 的有前途的生物标志物。本综述考察了 AD 中表观遗传标志物的现状,强调了它们在诊断和预后方面的相关性。APP、PSEN1 和 PSEN2 等基因中的 DNA 甲基化模式因其与 AD 病理学的强烈关联而受到关注。AD 患者中观察到特定 CpG 位点的 DNA 甲基化改变,表明它们在早期检测中的应用。组蛋白修饰,如乙酰化和甲基化,在 AD 中也在染色质重塑和基因表达调控中发挥关键作用。失调的组蛋白乙酰化和甲基化与 AD 进展有关,使这些修饰成为有价值的生物标志物。非编码 RNA,包括 microRNAs(miRNAs)和长非编码 RNA(lncRNAs),进一步促进了 AD 中的表观遗传调控。miRNAs 可以在转录后调节基因表达,并在 AD 中发现存在水平改变,而 lncRNAs 可以影响染色质结构和基因表达。这些非编码 RNA 存在于血液和脑脊液等生物流体中,使它们成为可及的、微创的生物标志物。检测和量化表观遗传修饰的技术进步推动了该领域的发展。下一代测序、亚硫酸氢盐测序和染色质免疫沉淀测定等技术提供了高灵敏度和特异性,使临床样本中表观遗传变化的详细分析成为可能。这些工具在将表观遗传学研究转化为临床实践中发挥了重要作用。本综述强调了表观遗传标志物在增强 AD 的早期诊断和预后中的潜力,为个性化治疗策略和改善患者预后铺平了道路。将这些生物标志物整合到临床工作流程中有望彻底改变 AD 的管理,为更好的疾病监测和干预提供希望。

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