Because our recent data showed major differences in seeding potency in vitro and propagation of distinct conformers of insoluble four-repeat AD tau aggregates in cells [3,27], we hypothesized that the structural organization of the microtubule-binding domain (MTBD) of misfolded tau could generate different conformers of misfolded tau (strains), which in turn could affect the rates of cognitive decline. This evidence concerns the gene MAPT and Alzheimer disease.