Presenilin (PS) provides the catalytic core of the γ-secretase complex. γ-Secretase activity
leads to generation of the amyloid β-peptide, a key event implicated in the pathogenesis of
Alzheimer disease. PS has ten hydrophobic regions, which can all theoretically form
membrane-spanning domains. Various topology models have been proposed, and the
prevalent view holds that PS has an eight-transmembrane (TM) domain organization;
however, the precise topology has not been unequivocally determined. Previous topological …