APOE and Brain atrophy: Using a P301S tauopathy mouse model on human APOE KI or APOE KO background Shi et al. found no changes at 3 months, but by 9 months the P301S/E4 mice had significantly more brain atrophy than P301S/E2, or P301S/E3, and that APOE KO mice were largely protected from this effect [147].