A mutation very close to the β-secretase cleavage site of APP. The Icelandic mutation A2T of Aβ42 turned out to be less pathogenic than the native sequence. The precursor APP A673T was the first APP variant discovered in humans reducing the risk of Alzheimer's disease. A2T as well affects γ-secretase cleavage, the mutant was an inefficient substrate in a cell-based assay of the enzyme.