Recent advances in understanding the genetics and underlying mechanisms of neurodegenerative diseases including prion diseases, Alzheimer’s, Parkinson’s, ALS and frontotemporal dementia have revealed overlaps of phenotypes, genetic risks and biological mechanisms across this spectrum of disorders. The “common mechanisms” include protein templating, glial and inflammatory mechanisms, new understanding of RNA-based toxicity and of toxicity associated with protein misfolding, and common downstream mechanisms affecting synaptic function. Moreover, because there appear to be common mechanisms at play, recent progress in therapeutic approaches targeting one of these disorders may have applicability across the whole range of disorders. This Keystone Symposia conference will enable the in-depth exploration of these various aspects of commonality across neurodegenerative disorders.