In P301S tau mice expressing mouse Apoe the loss of Trem2 (Sayed et al., 2018; Leyns et al., 2019) or the expression of loss-of-function R47H variant (Gratuze et al., 2020) decreased brain atrophy and neurodegeneration as well as microgliosis compared to control mice expressing wild type Trem2. Surprisingly, the deletion of Trem2 in the same P301S-tau model expressing human APOE4 isoform exacerbated tau-mediated brain atrophy (Gratuze et al., 2023). Here, APOE is linked to Brain atrophy.