Chromosome 14 MicroRNA Cluster Members in Brain-Derived Extracellular Vesicles Can Be Genotype-Associated Biomarker Candidates for Alzheimer's Disease and Frontotemporal Dementia

Background

The chromosome 14 microRNA cluster (C14MC) is the second largest microRNA (miRNA) cluster in the human genome, which is tightly regulated during early development and dysregulated in many disease conditions. Members of this cluster are reported to have important temporal and spatial roles in early development, especially in neurogenesis. Although extensively studied as cancer biomarkers, their potential as molecular signatures of neurodegenerative diseases (NDs) remains poorly understood. Given the importance of non-invasive or less-invasive biomarkers of dementia, brain-derived small extracellular vesicles (BDsEVs) represent a promising source of disease-associated miRNAs. BDsEVs can traverse the blood-brain barrier and potentially become a surrogate for molecular changes within the brain in accessible body fluids. We investigated whether BDsEV-associated C14MC miRNAs exhibit shared or disease-specific expression patterns in Alzheimer's disease (AD) and genetically defined subtypes of frontotemporal dementia (FTD).