Genetic and experimental evidence indicates that Aβ42 is the cause of AD pathogenesis [1, 2]: (1) FAD, although only 3–5% of all AD cases is caused by autosomal dominant mutations in APP, PS1, or PS2 that increase levels of Aβ42 or the Aβ42 : 40 ratio; (2) Down syndrome is caused by trisomy of chromosome 21 (the location of the APP gene), and is characterized by plaque deposition and dementia by the age 40; (3) Aβ42 is neurotoxic in vitro and in vivo. Here, APP is linked to Down syndrome.