Giuliani Angelica, Gaetani Simona, Sorgentoni Giulia, Agarbati Silvia, Laggetta Maristella, Matacchione Giulia, Gobbi Mirko, Rossi Tommaso, Galeazzi Roberta, Piccinini Gina, Pelliccioni Giuseppe, Bonfigli Anna Rita, Procopio Antonio Domenico, Albertini Maria Cristina, Sabbatinelli Jacopo, Olivieri Fabiola, Fazioli Francesca
Department of Clinical and Molecular Sciences, Università Politecnica Delle Marche, Ancona, Italy.
Neurology Department, IRCCS INRCA, Ancona, Italy.
Front Aging Neurosci. 2021 Mar 11;13:647015. doi: 10.3389/fnagi.2021.647015. eCollection 2021.
Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the growing population of elderly people, is still lacking minimally-invasive circulating biomarkers that could facilitate the diagnosis and the monitoring of disease progression. MicroRNAs (miRNAs) are emerging as tissue-specific and/or circulating biomarkers of several age-related diseases, but evidence on AD is still not conclusive. Since a systemic pro-inflammatory status was associated with an increased risk of AD development and progression, we focused our investigation on a subset of miRNAs modulating the inflammatory process, namely inflamma-miRNAs. The expression of inflamma-miR-17-5p, -21-5p, -126-3p, and -146a-5p was analyzed in plasma samples from 116 patients with AD compared with 41 age-matched healthy control (HC) subjects. MiR-17-5p, miR-21-5p, and miR-126-3p plasma levels were significantly increased in AD patients compared to HC. Importantly, a strong inverse relationship was observed between miR-21-5p and miR-126-3p, and the cognitive impairment, assessed by Mini-Mental State Examination (MMSE). Notably, miR-126-3p was able to discriminate between mild and severe cognitive impairment. Overall, our results reinforce the hypothesis that circulating inflamma-miRNAs could be assessed as minimally invasive tools associated with the development and progression of cognitive impairment in AD.
阿尔茨海默病（AD）是老年人口不断增长中最常见的神经退行性疾病，目前仍缺乏能够促进疾病诊断和病情进展监测的微创循环生物标志物。微小RNA（miRNA）正在成为多种与年龄相关疾病的组织特异性和/或循环生物标志物，但关于AD的证据仍不确凿。由于全身性促炎状态与AD发生和进展风险增加相关，我们将研究重点放在调节炎症过程的miRNA子集上，即炎症miRNA。分析了116例AD患者血浆样本中炎症miR-17-5p、-21-5p、-126-3p和-146a-5p的表达，并与41名年龄匹配的健康对照（HC）受试者进行比较。与HC相比，AD患者血浆中miR-17-5p、miR-21-5p和miR-126-3p水平显著升高。重要的是，观察到miR-21-5p和miR-126-3p与通过简易精神状态检查表（MMSE）评估的认知障碍之间存在强烈的负相关。值得注意的是，miR-126-3p能够区分轻度和重度认知障碍。总体而言，我们的结果强化了这样一种假设，即循环炎症miRNA可作为与AD认知障碍发生和进展相关的微创工具进行评估。
