APP and Alzheimer disease: From human genetics, dominant mutations causing early-onset familial AD reside either in APP or presenilin (catalytic sub-unit of γ-secretase), which alter the proteolytic processing of APP in ways either elevating the Aβ42/Aβ40 ratio or increasing the self-aggregation propensity of resultant Aβ peptides (De Jonghe, 2001; Selkoe, 2001; Chen et al., 2014).