Misfolded proteins accumulating in several neurodegenerative diseases (including Alzheimer’s, Parkinson’s and Huntington’s diseases) can cause aggregation of their native counterparts through a mechanism similar to the infectious prion protein’s induction of a pathogenic conformation onto its cellular isoform. Evidence for such a prion-like mechanism has now spread to the main misfolded proteins (SOD1 and TDP-43) implicated in Amyotrophic Lateral Sclerosis (ALS). The major neurodegenerative diseases may therefore have mechanistic parallels that provide a molecular pathway for non-cell autonomous disease spread within the nervous system.