Prions are proteins that access self-templating amyloid forms, which confer 
phenotypic changes that can spread from individual to individual within or 
between species. These infectious phenotypes can be beneficial, as with yeast 
prions, or deleterious, as with mammalian prions that transmit spongiform 
encephalopathies. However, the ability to form self-templating amyloid is not 
unique to prion proteins. Diverse polypeptides that tend to populate 
intrinsically unfolded states also form self-templating amyloid conformers that 
are associated with devastating neurodegenerative disorders. Moreover, two 
RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in 
amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in 
several yeast prion proteins. Can these proteins and the neurodegenerative 
diseases to which they are linked become 'infectious' too? Here, we highlight 
advances that define the transmissibility of amyloid forms connected with 
Alzheimer's disease, Parkinson's disease and Huntington's disease. Collectively, 
these findings suggest that amyloid conformers can spread from cell to cell 
within the brains of afflicted individuals, thereby spreading the specific 
neurodegenerative phenotypes distinctive to the protein being converted to 
amyloid. Importantly, this transmissibility mandates a re-evaluation of emerging 
neuronal graft and stem-cell therapies. In this Commentary, we suggest how these 
treatments might be optimized to overcome the transmissible conformers that 
confer neurodegeneration.