APOE and Alzheimer disease: Genetically humanised mice have also been used to assess the impact of a known modifier gene for AD, APOE4: ASO administration to double-humanised APOE (knock-in)/APPPS1 (transgenic) AD mice resulted in successfully reducing amyloid beta plaque pathology in both -E4/E4 (risk associated) and -E3/E3 (non-risk associated) mice, but only when applied before the onset of amyloid deposition, offering a valuable perspective on the utility of this treatment in the general population, and the need to carefully time treatments in human patients (Huynh et al. 2017).