PRNP and Alzheimer disease: Furthermore, PrPC on small EVs negatively regulates Aβ 1–42 uptake by neuronal cells [147] while, on the other hand, neuron-derived small EVs can be efficiently internalized by microglia and promote Aβ degradation, suggesting an overall protective effect of neuron-derived EVs against AD pathology [61,149], as opposed to microglia large EVs [21].