First, some aspects of AD are not fully captured by mouse models, such as the 5xFAD model used here, which display differences in plaque composition compared with the human brain and lack tau pathology.95 However, our use of humanized APOE TR (targeted replacement) mice96-99 appeared to substantially bridge the gap between human and mouse studies, resulting in high overlap with multiple human datasets. Here, MAPT is linked to Alzheimer disease.