MicroRNA Signature in Plasma-Derived Extracellular Vesicles in Frontotemporal Dementia

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.