Manzini Valeria, Cappelletti Pamela, Orefice Nicola S, Brentari Ilaria, Rigby Michael J, Lo Giudice Maria, Feligioni Marco, Rivabene Roberto, Crestini Alessio, Manfredi Francesco, Talarico Giuseppina, Bruno Giuseppe, Corbo Massimo, Puglielli Luigi, Denti Michela A, Piscopo Paola
Department of Neuroscience, Istituto Superiore Di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
Department of Biology and Biotechnology Charles Darwin, University of Rome "Sapienza", Rome, Italy.
Mol Neurobiol. 2025 Feb;62(2):2573-2586. doi: 10.1007/s12035-024-04386-z. Epub 2024 Aug 14.
Despite the efforts to identify fluid biomarkers to improve diagnosis of Frontotemporal dementia (FTD), only a few candidates have been described in recent years. In a previous study, we identified three circulating miRNAs (miR-92a-3p, miR-320a and miR-320b) differentially expressed in FTD patients with respect to healthy controls and/or Alzheimer's disease (AD) patients. Now, we investigated whether those changes could be due to miRNAs contained in neuron-derived extracellular vesicles (NDEVs). We also evaluated miRNAs content in total plasma EVs and in CSF samples. The analysis of plasma NDEVs carried out on 40 subjects including controls (n = 13), FTD (n = 13) and AD (n = 14) patients, showed that both miR-92a-3p and miR-320a levels were triplicated in the FTD group if compared with CT and AD patients. Increased levels of the same miRNAs were found also in CSF derived from FTD group compared to CTs. No differences were observed in expression levels of miR-320b among the three groups. Worthy of note, all miRNAs analysed were increased in an FTD cell model, MAPT IVS10 + 16 neurons. Our results suggest that miR-92a and miR-320a in NDEVs could be proposed as FTD biomarkers.
尽管人们努力寻找可改善额颞叶痴呆（FTD）诊断的体液生物标志物，但近年来仅有少数几种候选物被报道。在之前的一项研究中，我们鉴定出三种循环miRNA（miR-92a-3p、miR-320a和miR-320b）在FTD患者中相对于健康对照和/或阿尔茨海默病（AD）患者存在差异表达。现在，我们研究了这些变化是否可能归因于神经元衍生的细胞外囊泡（NDEVs）中所含的miRNA。我们还评估了总血浆细胞外囊泡（EVs）和脑脊液样本中的miRNA含量。对包括对照组（n = 13）、FTD患者（n = 13）和AD患者（n = 14）在内的40名受试者进行的血浆NDEVs分析表明，与对照组和AD患者相比，FTD组中miR-92a-3p和miR-320a的水平均增加了两倍。与对照组相比，FTD组脑脊液中相同miRNA的水平也有所升高。三组间miR-320b的表达水平未观察到差异。值得注意的是，在FTD细胞模型MAPT IVS10 + 16神经元中，所有分析的miRNA水平均升高。我们的结果表明，NDEVs中的miR-92a和miR-320a可被提议作为FTD的生物标志物。
