Recent data have shown the importance of genetic background in the design of mouse models of Alzheimer’s disease.14 Several studies show differences in tau pathology accumulation in the rTg4510 mouse model of tauopathy with different backgrounds.15,16 In a tau seeding paradigm in rat transgenic models, Smolek et al. 17 also find genetic background heterogeneity. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.