Second, a mutation in human APP, which reduces cleavage by BACE1 (Jonsson et al, 2012), leads to a reduction in cerebral Aβ of approximately 20%, with carriers showing lifelong protection against AD and cognitive decline (although issues with the mutation affecting aggregation of Aβ peptides cannot be fully excluded) (Benilova et al, 2014; Maloney et al, 2014). Here, APP is linked to Alzheimer disease.