Neurodegenerative diseases are characterized by the progressive decline of neuronal functions in a spatiotemporal fashion, leading to the worsening of neurological symptoms, in some cases, with devastating speed. This is accompanied by the gradual intensity of neuropathological findings from more to less affected regions in the nervous system. The molecular pathway driving progressive decline of disease symptoms and pathology is not yet understood. However, the amplification of pathological protein assemblies, which spread from cell-to-cell, may well explain these phenomena. We will bring together neurologists, neuropathologists and basic scientists from a wide variety of neurodegenerative diseases to discuss the implications of these mechanisms for building disease models and therapeutic strategies. We will also address the similarities and differences between the different classes of neurodegeneration, comparing to prototypical prion diseases. Lastly, we will examine the role of inflammation and cellular stress in potentiating the initiation and spreading of pathology.