Extracellular vesicles (EVs) are lipid bilayer-delimited pieces of cells that are released from the plasma membrane as "ectosomes" and from the endosomal system as "exosomes." EVs serve both to dispose of toxic materials and to facilitate intercellular communication, so they have many roles to play in disease, including neurodegenerative diseases such as Alzheimer's. Although the long-distance, inter-organ actions of EVs are an exciting topic of research, EVs in solid tissues are most likely to act locally, near the site of release. Our group has adapted a rigorous method for EV separation from tissues. Here, we discuss this method and some of the challenges and opportunities it presents. We then examine molecular profiling of EVs from brain of Alzheimer's disease patients and matched controls and assess possible contributions of APOE genotype. We review the implications of our findings for peripheral biomarkers of disease, using single-particle characterization technologies. All results are shared in the context of the "Minimal Information for Studies of EVs" (MISEV), the consensus document on best practices in the field that was issued by the International Society for Extracellular Vesicles and most recently updated as MISEV2018 (Théry and Witwer, et al, J Extracell Vesicles, 2018). We expect that rigorous and reproducible EV science will continue to develop and contribute to personalized medicine in the coming years.
1. Explain the challenges and opportunities in studying extracellular vesicles in tissue
2. Identify associations between Alzheimer's disease and EV cargo
3. Introduce rigorous approaches to EV separation and characterization