Chacón Tatiana, Hernández Hernán G
Dentistry Faculty, Universidad Santo Tomas, Bucaramanga, Colombia.
Health Faculty, Universidad Autónoma de Manizales, Antigua Estación del Ferrocarril, Manizales, Colombia.
J Alzheimers Dis Rep. 2025 May 7;9:25424823251341176. doi: 10.1177/25424823251341176. eCollection 2025 Jan-Dec.
Chronic systemic inflammation is implicated in Alzheimer's disease (AD) pathogenesis and has measurable effects on blood cells. There is increasing interest in non-invasive diagnostic tools that use blood-based biomarkers for AD, such as DNA methylation. Notably, DNA methylation changes in blood are also linked to systemic inflammation. The evaluation of DNA methylation profiles in peripheral blood leukocytes as potential biomarkers for AD is promising.
To determine DNA methylation patterns in blood for AD, and to explore specific blood CpG sites that act as surrogates for brain-tissue methylation.
DNA methylation data from peripheral blood leukocytes of AD patients and controls were obtained from the Gene Expression Omnibus (GSE59685 and GSE53740). Differential methylation analysis was performed for individual CpGs Differentially methylated positions (DMPs) and regions with multiple probes (DMRs) and the intersection analysis of DMPs and DMRs was conducted. Functional enrichment analysis highlights relevant biological processes. Furthermore, previously validated specific CpGs used as surrogate of brain tissue were explored.
DNA methylation patterns included , , , and top genes ordered by statistical significance were found in the intersection of DMP and DMR. Differential methylation analyses revealed differentially methylated genes including , , , , , , and . Gene enrichment analysis showed immune processes and intracellular signaling disruptions. Surrogate genes from brain found differentially methylated were and .
This study identified DNA methylation patterns in peripheral blood leukocytes as potential biomarkers for AD. These findings offer insights into epigenetic mechanisms associated with systemic peripheral inflammation in AD.
慢性全身炎症与阿尔茨海默病（AD）的发病机制有关，并且对血细胞有可测量的影响。人们对使用基于血液的生物标志物（如DNA甲基化）进行AD的非侵入性诊断工具越来越感兴趣。值得注意的是，血液中的DNA甲基化变化也与全身炎症有关。评估外周血白细胞中的DNA甲基化谱作为AD的潜在生物标志物很有前景。
确定血液中AD的DNA甲基化模式，并探索作为脑组织甲基化替代物的特定血液CpG位点。
从基因表达综合数据库（GSE59685和GSE53740）中获取AD患者和对照的外周血白细胞DNA甲基化数据。对单个CpG进行差异甲基化分析，进行差异甲基化位点（DMPs）和具有多个探针的区域（DMRs）分析以及DMPs和DMRs的交集分析。功能富集分析突出相关的生物学过程。此外，还探索了先前验证的用作脑组织替代物的特定CpGs。
DNA甲基化模式包括 ， ， ，并且在DMP和DMR的交集中发现了按统计显著性排序的前 个基因。差异甲基化分析揭示了差异甲基化基因，包括 ， ， ， ， ， ，和 。基因富集分析显示免疫过程和细胞内信号传导中断。从大脑中发现的替代基因 和 存在差异甲基化。
本研究确定外周血白细胞中的DNA甲基化模式作为AD的潜在生物标志物。这些发现为AD中与全身外周炎症相关的表观遗传机制提供了见解。
