The promise and challenges of extracellular vesicles in the diagnosis of neurodegenerative diseases

Extracellular vesicles (EVs) have emerged as essential means of intercommunication for all cell types, and their role in CNS physiology is increasingly appreciated. Accumulating evidence has demonstrated that EVs play important roles in neural cell maintenance, plasticity, and growth. However, EVs have also been demonstrated to spread amyloids and inflammation characteristic of neurodegenerative disease. Such dual roles suggest that EVs may be prime candidates for neurodegenerative disease biomarker analysis. This is supported by several intrinsic properties of EVs: Populations can be enriched by capturing surface proteins from their cell of origin, their diverse cargo represent the complex intracellular states of the cells they derive from, and they can pass the blood-brain barrier. Despite this promise, there are important questions outstanding in this young field that will need to be answered before it can fulfill its potential. Namely, overcoming the technical challenges of isolating rare EV populations, the difficulties inherent in detecting neurodegeneration, and the ethical considerations of diagnosing asymptomatic individuals. Although daunting, succeeding to answer these questions has the potential to provide unprecedented insight and improved treatment of neurodegenerative disease in the future.