The effects of rh Bri2 BRICHOS R221E on Trem2 and Apoe, as on Clu, Gfap, Igfbp5 and Prdx6 are likely related to the AD-like pathology in the AppNL-G-F mice, since rh Bri2 BRICHOS R221E treatment of WT mice caused no changes in Clu, Gfap, Igfbp5 and Prdx6, Trem2 or Apoe expression levels (Fig. 8A and Supplementary Fig. 4). Here, APOE is linked to Alzheimer disease.