The expression levels of the PIGs Trem2 and ApoE, both known to be associated with risk of developing AD, were increased in AppNL-G-F mice compared to WT mice, and treatment with rh Bri2 BRICHOS R221E resulted in a further increase, ca. 20% (Supplementary Fig. 4). The gene discussed is ITM2B; the disease is Alzheimer disease.