Evidence for the association between Aβ and AD largely come from the early onset of AD-type pathology in individuals with extra dosage due to chromosome 21 trisomy19,20, as well as from familial AD cases with mutations close to the γ secretase cleavage site of amyloid precursor protein (APP)21,22 and before the β secretase cleavage site at the N-terminus of Aβ23, or with Aβ variants that are more aggregation-prone or follow an altered aggregation pathway24–27. Here, APP is linked to Alzheimer disease.