Extracellular vesicles (EVs) are secreted by any neuronal cells in the central nervous system (CNS) for molecular clearance, cellular communications and disease spread in multiple neurodegenerative diseases, including Alzheimer’s disease (AD), although their exact molecular mechanism is poorly understood. We hypothesize that high-resolution proteomic profiling of EVs separated from animal models of AD would determine the composition of EV contents and their cellular origin.