Plasma-Derived miRNAs as Fluid Biomarkers to Differentiate Alzheimer’s and Frontotemporal Dementia

Abstract Alzheimer’s disease (AD) and Frontotemporal Dementia (FTD) are complex neurodegenerative disorders, often sharing overlapping symptoms. Non-coding RNAs may be involved in pathological processes in these conditions, hence the study of miRNAs isolated from plasma-derived extracellular vesicles (EVs) could provide exploratory insights into the molecular background. The main aim of this work was to identify shared deregulated miRNAs presenting different expression patterns in the two pathologies. A selection of the identified deregulated miRNAs was further studied with the purpose of identifying their mRNA targets and generating hypotheses on their potential pathological involvement. A total of 340 and 291 differentially expressed miRNAs were found in FTD and AD, respectively. Among the commonly deregulated miRNAs with opposite expression patterns between the two conditions, miR-638 emerged as a candidate of interest, showing consistent patterns across our experimental analyses. Nevertheless, these findings are preliminary and intended to be interpreted cautiously, requiring validation in larger cohorts. In addition, the expression of two of its predicted targets in peripheral blood mononuclear cells (PBMCs) appeared to align with miR-638 expression in the same cell type and may reflect potential differences in underlying brain pathological states.