Vargas-Rondón Natalia, González-Giraldo Yeimy, García Fonseca Ángela Y, Gonzalez Janneth, Aristizabal-Pachon Andrés Felipe
Experimental and Computational Biochemistry, Department of Nutrition and Biochemistry, Faculty of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
Front Aging Neurosci. 2025 Jan 15;16:1524622. doi: 10.3389/fnagi.2024.1524622. eCollection 2024.
Mild cognitive impairment (MCI) is characterized by a decline in cognitive functioning without significant interference in daily activities. Its high heterogeneity and elevated conversion rate to dementia pose challenges for accurate diagnosis and monitoring, highlighting the urgent need to identify methodologies focused on the early detection and intervention of MCI. Due to their biological characteristics, microRNAs (miRNAs) are potential candidates as non-invasive molecular markers for the identification and assessment of MCI progression. Therefore, in this study, we conducted a meta-analysis to identify the miRNAs commonly deregulated in MCI, focusing on expression profiles in plasma, serum, and extracellular vesicle samples. Our analysis identified eight upregulated miRNAs, including hsa-miR-149-3p, and four downregulated miRNAs, such as Let-7f-5p. Notably, hsa-miR-149-3p emerged as a central node in interaction networks, suggesting its crucial role in regulating cellular processes relevant to MCI. Additionally, pathway analysis revealed significant enrichment in biological processes associated with transcriptional regulation and neurodegeneration. Our results underscore the potential of circulating miRNAs as non-invasive molecular markers for MCI and open the possibility for new methodologies that enable more accurate diagnosis and monitoring of disease progression. Validating the expression of miRNAs such as hsa-miR-149-3p and Let-7f-5p, along with identifying their functional role in the specific context of MCI, is essential to establish their biological relevance. This work contributes to the understanding of the miRNA profile in mild cognitive impairment using easily accessible samples, which could be useful for the development of various strategies aimed at preventing or delaying MCI in individuals at risk of developing dementia, including Alzheimer's disease.
轻度认知障碍（MCI）的特征是认知功能下降，但对日常活动没有显著干扰。其高度的异质性和向痴呆症的高转化率给准确诊断和监测带来了挑战，凸显了迫切需要确定专注于MCI早期检测和干预的方法。由于其生物学特性，微小RNA（miRNA）作为用于识别和评估MCI进展的非侵入性分子标记物具有潜在可能性。因此，在本研究中，我们进行了一项荟萃分析，以确定在MCI中普遍失调的miRNA，重点关注血浆、血清和细胞外囊泡样本中的表达谱。我们的分析确定了8种上调的miRNA，包括hsa-miR-149-3p，以及4种下调的miRNA，如Let-7f-5p。值得注意的是，hsa-miR-149-3p在相互作用网络中成为一个中心节点，表明其在调节与MCI相关的细胞过程中起关键作用。此外，通路分析显示在与转录调控和神经退行性变相关的生物学过程中显著富集。我们的结果强调了循环miRNA作为MCI非侵入性分子标记物的潜力，并为能够更准确诊断和监测疾病进展的新方法开辟了可能性。验证hsa-miR-149-3p和Let-7f-5p等miRNA的表达，以及确定它们在MCI特定背景下的功能作用，对于确立其生物学相关性至关重要。这项工作有助于利用易于获取的样本了解轻度认知障碍中的miRNA谱，这对于制定旨在预防或延缓有患痴呆症风险个体（包括阿尔茨海默病患者）的MCI的各种策略可能是有用的。
