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Updated: Jun 17, 2025
Harnessing the Power of MicroRNA Cargoes in Small Extracellular Vesicles Released from Fresh-Frozen Human Brain Sections
Published on: November 8, 2024
miR-92a-3p and miR-320a are Upregulated in Plasma Neuron-Derived Extracellular Vesicles of Patients with
Valeria Manzini1,2, Pamela Cappelletti3, Nicola S Orefice4,5,6
1Department of Neuroscience, Istituto Superiore Di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
Abstract:
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.
Insights
Frontotemporal dementia (FTD) diagnosis may be improved by neuron-derived extracellular vesicle (NDEV) biomarkers. Specifically, miR-92a and miR-320a levels in NDEVs are significantly increased in FTD patients, suggesting their potential diagnostic utility.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Molecular Biology
Background:
- Frontotemporal dementia (FTD) diagnosis lacks reliable fluid biomarkers.
- Previous research identified circulating microRNAs (miRNAs) differentially expressed in FTD.
- The origin of these differentially expressed miRNAs, particularly in neuron-derived extracellular vesicles (NDEVs), remains unclear.
Purpose of the Study:
- To investigate if altered miRNA levels in FTD are associated with neuron-derived extracellular vesicles (NDEVs).
- To evaluate miRNA content in plasma extracellular vesicles (EVs) and cerebrospinal fluid (CSF) in FTD patients.
- To explore the potential of specific miRNAs within NDEVs as diagnostic biomarkers for FTD.
Main Methods:
- Analysis of plasma NDEVs from 40 subjects (13 controls, 13 FTD, 14 Alzheimer's disease patients).
- Quantification of miR-92a-3p, miR-320a, and miR-320b levels in plasma NDEVs, total plasma EVs, and CSF.
- Assessment of miRNA expression in an FTD cell model (MAPT IVS10+16 neurons).
Main Results:
- Plasma NDEVs showed tripled levels of miR-92a-3p and miR-320a in FTD patients compared to controls and AD patients.
- Increased levels of miR-92a-3p and miR-320a were also observed in CSF from FTD patients.
- No significant differences in miR-320b levels were found among the groups.
- All analyzed miRNAs were elevated in the FTD cell model.
Conclusions:
- miR-92a and miR-320a within neuron-derived extracellular vesicles (NDEVs) show potential as diagnostic biomarkers for Frontotemporal dementia (FTD).
- These findings highlight the importance of NDEVs as a source for FTD fluid biomarkers.
- Further validation is warranted to establish their clinical utility in FTD diagnosis.
