Fig. 13

Model of different pathomechanism in the tested FAD mutants. Amino acid substitutions around the β-secretase cleavage site lead to an increase in Aβ peptides starting at position 1, mainly Aβ 1–17. The FAD mutations around the α-secretase cleavage site lead to a higher amount of N-terminally truncated Aβ peptides starting at position 5 as well as decreased sAPPα production while the mutation at the γ-secretase site showed the strongest change in the ratio of Aβ40/Aβ42. Furthermore, the APP Iberian showed a reduced synaptogenic activity whereas APP Iowa was localized to a higher amount in endosomes