To date, AD research has mainly focused on early-onset familial cases driven by mutations on APP or PSEN. Although they only comprise approximately 5% of AD cases, the cause of pathology seems to be quite straightforward, as mutations in these genes are well known to induce either increases in total Aβ production or increases in the ratio of toxic Aβ species, eventually resulting in neurodegeneration [46]. Here, APP is linked to Alzheimer disease.