The differences in pathology between our APOE4- and APOE3-tauopathy mice are in line with the observations in human AD patients that show those with the APOE4 genotype have considerably more microgliosis51,79 and astrogliosis,83 Tau pathology,84–86 neurodegeneration,25,87 and myelin deficits26 than AD patients with the APOE3 genotype. This evidence concerns the gene MAPT and tauopathy.