The role of extracellular vesicles in neurodegenerative diseases.

Neurodegenerative disorders such as Alzheimer’s (AD), Parkinson’s (PD) and prion diseases are associated with proteins that misfold and deposit in the brain. Many cell types, including neurons, release extracellular vesicles (EVs) which include microvesicles and exosomes. EVs have been shown to be involved in processing of proteins such as APP, α-synuclein, and PrP which are those involved in AD, PD and prion diseases respectively. Roles for these vesicles include cell-cell signalling, removal of unwanted proteins, and transfer of pathogens (including prion-like misfolded proteins) between cells. Our group has shown that EV’s contain distinct processed forms of these proteins and that, in the case of prion disease, they contain the transmissible form of the misfolded protein. In addition to their protein content these vesicles have recently been shown to contain genetic material in the form of protein coding (mRNA) and noncoding RNA species. We have analysed the protein and genetic cargo of EVs from a number of cell types and using deep sequencing, characterised the RNA cargo of these vesicles. As exosomes can be isolated from circulating fluids such as serum, urine, and cerebrospinal fluid (CSF), they provide a potential source of biomarkers for neurological conditions. This talk will review the roles these vesicles play in neurodegenerative disease and highlight their potential in diagnosing these disorders through analysis of their RNA content.