Overview of dominantly inherited mutations in presenilin 1. Presenilin contains nine transmembrane domains. The presenilin 1 mutations (red circles) are scattered over the protein, but most are in the hydrophobic domains of the protein. Green and yellow circles indicate whether the effect of the mutation on amyloid-beta (Aβ) production has been investigated: green, mutations that decrease Aβ40 production; yellow, mutations that increase Aβ42 production. In all cases, an increase of the Aβ42/Aβ40 ratio has been found.