Rat and human APP differ by 3 amino acids in the Aβ region (Figure 1A): since aggregated forms of Aβ are by and large considered the main pathogenic molecule in AD and given that human Aβ may have higher propensity to form toxic Aβ species as compared to rodent Aβ, together with the protective and Swedish mutations we introduced mutations to ‘humanize’ the rat Aβ sequence. Here, APP is linked to Alzheimer disease.