Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of The Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940, Leioa, Spain.
BioCruces Bizkaia Health Research Institute, Barakaldo, Spain.
Mol Neurobiol. 2019 Dec;56(12):8376-8391. doi: 10.1007/s12035-019-01676-9. Epub 2019 Jun 25.
Late-onset Alzheimer's disease (LOAD) is a high-occurrence neurological disorder but the difficulty in identifying precise and early biomarkers has complicated the understanding of the disease and the development of new treatments. In this sense, important knowledge is emerging regarding novel molecular and biological candidates with diagnostic potential, including microRNAs (miRNAs), which have a key role in gene repression. The aim of this systematic review was to define the role of miRNAs' expression as biomarkers for LOAD both in brain tissues, which could help understand the biology of the disease, and circulating tissues, which could serve as non-invasive markers of the pathology. A systematic search was performed in Web of Science and PubMed using the keywords ((Alzheimer or Alzheimer's) and (microRNA or microRNAs or miRNA or miRNAs or miR)) until August 2018 to retrieve all articles that presented independent original data evaluating the impact of miRNA expression on the development of LOAD in human population. A total of 90 studies investigating the role of miRNAs' expression in the development of LOAD were identified. While other widely studied miRNAs such as hsa-miR-146a presented contradictory results among studies, deregulation in brain tissue of seven miRNAs, hsa-miR-16-5p, hsa-miR-34a-5p, hsa-miR-107, hsa-miR-125-5p, hsa-miR-132-3p, hsa-miR-181-3p, and hsa-miR-212-3p, was consistently identified in LOAD patients. Their role in the disease could be mediated through the regulation of key pathways, such as axon guidance, longevity, insulin, and MAPK signaling pathway. However, regarding their role as non-invasive biomarkers of LOAD in fluids, although the limited results available are promising, further studies are required.
迟发性阿尔茨海默病（LOAD）是一种高发性神经退行性疾病，但由于难以确定准确和早期的生物标志物，这使得人们对该疾病的理解和新疗法的开发变得复杂。在这方面，关于具有诊断潜力的新型分子和生物学候选物的重要知识正在不断涌现，包括 microRNAs（miRNAs），它们在基因抑制中起着关键作用。本系统评价的目的是定义 miRNA 表达作为 LOAD 生物标志物的作用，包括脑组织中的 miRNA 表达，这有助于了解疾病的生物学特性，以及循环组织中的 miRNA 表达，作为病理学的非侵入性标志物。我们在 Web of Science 和 PubMed 上使用关键词（(Alzheimer 或 Alzheimer's) 和 (microRNA 或 microRNAs 或 miRNA 或 miRNAs 或 miR)）进行了系统搜索，直到 2018 年 8 月，以检索所有提出独立原始数据评估 miRNA 表达对人类 LOAD 发展影响的文章。共确定了 90 项研究 miRNA 表达在 LOAD 发展中的作用。虽然其他广泛研究的 miRNAs，如 hsa-miR-146a，在研究中存在相互矛盾的结果，但在 LOAD 患者的脑组织中，有七种 miRNAs（hsa-miR-16-5p、hsa-miR-34a-5p、hsa-miR-107、hsa-miR-125-5p、hsa-miR-132-3p、hsa-miR-181-3p 和 hsa-miR-212-3p）的表达出现失调。它们在疾病中的作用可能是通过调节关键途径，如轴突导向、长寿、胰岛素和 MAPK 信号通路来介导的。然而，关于它们作为 LOAD 液体中非侵入性生物标志物的作用，尽管目前可用的有限结果很有希望，但仍需要进一步的研究。
