Accumulating evidence implicates the transmission of aggregation prone proteins in the etiology of neurodegenerative diseases. Extracellular vesicles such as exosomes have been shown to be important not only for the secretion of proteins associated with neurodegeneration, but also assisting in their misfolding. We have investigated the trafficking of both α-synuclein and Amyloid precursor protein (APP) in extracellular vesicles. Ubiquitinated forms of both α-synuclein and APP are trafficked in the cell on endosomes that can result in the loading of each into exosomes. Here we will report our findings investigating the extracellular trafficking of both proteins. We show that (i) risk factors associated with Parkinson’s disease can promote the loading of α-synuclein into exosomes and demonstrate how these exosomes are pathogenic using in vivo mouse models; (ii) dysregulation of degradation pathways within a cell can result in the trafficking of APP into extracellular vesicles. Together our findings highlight mechanisms that can promote the release of proteins associated with neurodegeneration, resulting in the transmission of disease within the body.