APP and Alzheimer disease: 3 There are several known mutations of APP andthe presenilin proteins of the γ-secretase that give rise toAD, either via an increased level of production of Aβ or viaits propensity to aggregate.4−6 One familial form of AD is theArctic mutation of APP (E693G), which deviates from many other knownAPP mutations by the rapid formation of stable toxic Aβ oligomers.The pathogenesis associated with the Arctic mutation resembles thatof wild type Aβ, but the progression is faster.7−9