Fig. (1).

Schematic illustration of APP protein and its Aβ product after cleavage by α-, β- and γ-secretases. β- and γ-secretase cleaves on the N- and C-terminal ends of the Aβ region respectively. γ-Secretase cleavage yields a 39–43 amino acid product. Long and more fiblillogenic 42–43 amino acid Aβ species are implicated in AD pathogenesis and may seed the formation of Aβ40 fibrils. Mutations in the APP gene and in genes encoding proteins known as presenilins increase the production of long Aβ. Presenilins-1 and −2 is thought function as γ-secretases (for a review, see [142]).