Mendioroz Iriarte Maite, Pulido Fontes Laura, Méndez-López Iván
Complejo Hospitalario de Navarra, Pamplona, Navarra, España; Navarrabiomed, Pamplona, Navarra, España.
Complejo Hospitalario de Navarra, Pamplona, Navarra, España; Navarrabiomed, Pamplona, Navarra, España.
Med Clin (Barc). 2015 May 21;144(10):457-64. doi: 10.1016/j.medcli.2014.03.023. Epub 2014 Jun 3.
DNA methylation is an epigenetic mechanism that controls gene expression. In Alzheimer's disease (AD), global DNA hypomethylation of neurons has been described in the human cerebral cortex. Moreover, several variants in the methylation pattern of candidate genes have been identified in brain tissue when comparing AD patients and controls. Specifically, DNA methylation changes have been observed in PSEN1 and APOE, both genes previously being involved in the pathophysiology of AD. In other degenerative dementias, methylation variants have also been described in key genes, such as hypomethylation of the SNCA gene in Parkinson's disease and dementia with Lewy bodies or hypermethylation of the GRN gene promoter in frontotemporal dementia. The finding of aberrant DNA methylation patterns shared by brain tissue and peripheral blood opens the door to use those variants as epigenetic biomarkers in the diagnosis of neurodegenerative diseases.
DNA甲基化是一种控制基因表达的表观遗传机制。在阿尔茨海默病（AD）中，人类大脑皮层中已发现神经元存在全基因组DNA低甲基化现象。此外，在比较AD患者和对照的脑组织时，已在候选基因的甲基化模式中鉴定出几种变异。具体而言，已在早老素1（PSEN1）和载脂蛋白E（APOE）中观察到DNA甲基化变化，这两个基因此前均参与了AD的病理生理学过程。在其他退行性痴呆中，关键基因的甲基化变异也有报道，如帕金森病和路易体痴呆中α-突触核蛋白（SNCA）基因的低甲基化，或额颞叶痴呆中GRN基因启动子的高甲基化。脑组织和外周血中共享的异常DNA甲基化模式的发现，为将这些变异用作神经退行性疾病诊断中的表观遗传生物标志物打开了大门。
