To generate this mouse model, the homozygous human APOE4 or APOE3 knockin mice previously generated in our lab49 were cross-bred with a widely utilized tauopathy mouse model (PS19 line) that expresses P301S mutant human microtubule-associated protein Tau (MAPT).50 The resulting PS19-E4 and PS19-E3 mice were used in this study. Here, APOE is linked to tauopathy.