While autosomal dominant mutations in α-syn, TDP-43, and tau are causal for only a minority of neurodegenerative disease cases, they nevertheless can provide key insights into the development of sporadic forms of neurodegeneration, as these diseases are also associated with α-syn, TDP-43, and/or tau aggregation but yet occur in the absence of mutations. This evidence concerns the gene MAPT and neurodegenerative disease.