Structure and dynamics of γ-secretase with presenilin 2 compared to presenilin 1.

Severe early-onset familial Alzheimer's disease (FAD) is caused by more than 200 different mutations in the genes coding for presenilin, the catalytic subunit of the 4-subunit protease complex γ-secretase, which cleaves the C99 fragment of the amyloid precursor protein (APP) to produce Aβ peptides. γ-Secretase exists with either of two homologues, PS1 and PS2. All cryo-electron microscopic structures and computational work has so far focused on γ-secretase with PS1, yet PS2 mutations also cause FAD.