APOE and age-related macular degeneration: Indeed, the targeted replacement mice expressing the human APOE4 (TRE4), and not APOE2 (TRE2), accumulate most lipids in Bruchs membrane compared to APOE3-expressing TRE3 mice (Malek et al. 2005), although APOE4-allele plays a protective role in human AMD (McKay et al. 2011).