Rat App was humanized for the following reasons: 1) aggregated or oligomeric forms of Aβ are by and large considered the main pathogenic entity in AD; 2) human Aβ has higher propensity to form toxic Aβ species as compared to rodent Aβ; 3) as discussed above, TREM2 pathogenic variants may facilitate neurodegeneration by increasing human Aβ-mediated neurotoxicity, Here, we characterize the effect of Trem2R47H on human Aβ levels and APP processing. The gene discussed is APP; the disease is Alzheimer disease.