FIGURE 6: Mechanism of presenilin FAD mutations. (A) Model depicting impaired processivity in the Aβ40 and Aβ42 product lines causing relative increases in the generation of the longer Aβ species Aβ42 and Aβ43. Structural instability of FAD mutant presenilin leads to impaired processivity manifested by faster dissociation rates and premature release of long Aβ such as Aβ42 from the enzyme. (B) Presenilin FAD mutations cause a mispositioning of C99 as shown by altered interactions of the substrate cleavage domain with the enzyme. Residues that were identified to show increased or decreased interactions with two different PS1 FAD mutants are shown in red and blue, respectively. Yellow asterisk indicates a FAD mutation.