There are provided, inner alia, compounds and methods for lowering total AB peptide production by inhibiting the catalytic activity of gamma-secretase. Since all of the major AB peptide variants, including the pathogenic AB42 as known in the art, are ultimately generated by gamma-secretase-mediated proteolysis of APP-C99 (i.e., the beta-secretase-mediated cleavage product of the amyloid protein precursor IAPPI), one approach to therapeutic intervention (e.g., intervention in Alzheimer's Disease, AD) relates to lowering total AB peptide production by inhibiting the catalytic activity of gamma-secretase.