Extracellular RNA in Alzheimer’s disease

Abstract

Extracellular vesicles (EVs) are released from all cells and represent a heterogeneous mixture of species, differing in size, function, cargo and cellular origin. EVs contain a diverse cargo, including a multitude of, predominantly non-coding, RNA species (exRNA). Alterations in exRNA have been associated with various diseases, including Alzheimer’s disease (AD). AD is a progressive neurodegenerative disease of unknown aetiology which is often associated with diagnosis in the later stages of disease and poor therapeutic options. Given the huge number of people affected by AD, both directly and indirectly, the disease has a significant social and economic burden. Thus, there is a critical need for novel mechanistic and therapeutic avenues of discovery. Hence exRNA “fingerprints” may assist with earlier, more reliable diagnoses and greater insight into disease mechanisms. However, given the large variation in study populations (stage of AD, genetic background) and analysis methods (e.g., biofluids, RNA extraction protocols), there is limited concordance in the published literature. Most studies focus on miRNA alterations, and several independent studies have reported downregulation of miR-125b, miR-29b, miR-342, miR-107, miR-142 and miR-15b in plasma/serum/blood and also miR-29c, miR-127 and miR-139 in CSF. Going forward, as exRNA consortia are assembled, protocols are standardised and novel technologies are leveraged, this field holds great promise