Studies focused on expanding our understanding of molecular mechanisms underlying prion-like propagation of pathogenic protein aggregates formed by mHTT, tau, α-synuclein, TDP-43, and SOD1, and how aggregate spread is causally linked to neuronal loss, will lend insight into new therapeutic strategies that can impede progression of these fatal neurodegenerative diseases. This evidence concerns the gene MAPT and neurodegenerative disease.