This work aimed to identify a specific miRNA signature to better characterize FTD pathology and revealed that miR-365a-3p and miR-212 were significantly down-regulated in FTD.
Abstract
Background: Frontotemporal dementia (FTD) is a neurodegenerative disease that shares numerous clinical features with other forms of dementia. In this context, non-coding RNAs, specifically microRNAs (miRNAs), represent a promising tool for differential diagnosis. Since these miRNAs can be isolated from circulating extracellular vesicles (EVs) in peripheral blood, they provide a direct insight into FTD-specific molecular processes. Consequently, while EV-contained miRNAs hold potential as disease-specific biomarkers, investigating their relative target genes can help elucidate their precise functional roles. Aim: This work aimed to identify a specific miRNA signature to better characterize FTD pathology. Methods: Building on a previous Next-Generation Sequencing (NGS) analysis, three candidate miRNAs were selected for validation in both EVs and peripheral blood mononuclear cells (PBMCs) of FTD patients. Subsequently, the predicted target genes of two of these miRNAs were validated in PBMCs to assess their expression levels. Results: Our findings revealed that miR-365a-3p and miR-212 were significantly down-regulated in FTD. Conclusions: Together with their target genes, these miRNAs are involved in cell cycle and apoptotic pathways, suggesting a potential role in the pathological mechanisms of the disease.
Findings suggest EV-miR-223-5p as a candidate marker of the progressive phenotype and EV-miR-155-5p as a disease indicator, which is hypothesis-generating and requires validation in larger, longitudinal cohorts.
Oana Vrînceanu, D. Manu, S. Maier et al.· International Journal of Mol...· 1 citation
The EV miRNAs, specifically, hsa-let-7e-5p, hsa-miR-19b-3p, hsa-miR-24-3p, and hsa-miR-331-5p are promising candidates for PD diagnosis as they are associated with regulatory pathways involved in PD pathogenesis.
The findings support the potential relevance of vesicular-associated miRNAs as candidates of age-related cognitive dysfunctions, although for clinical practice some methodological issues may arise, i.e., the feasibility of total EVs extraction.
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Preliminary observations should be interpreted with caution, given the exploratory nature and modest cohort size, but the selective downregulation of EV-miR-223-5p and EV-miR-155-5p may tentatively suggest candidate molecular signatures warranting further interrogation.
Oana Vrînceanu, S. Maier, D. Manu et al.· Cells· 0 citations
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