Acknowledging the existence of widely-used conformation-specific tau antibodies (112) and noting heterogeneity in PrP structure in prion strains (113), a conceptual approach deriving from prion disease is to consider (i) alternative folding outcomes as key determinants of heterogeneity in clinical presentation of tauopathies and (ii) propagation of tau conformers by templating as a mechanism underpinning the spread of disease-associated forms. The gene discussed is MAPT; the disease is tauopathy.