Thec-secretase complex mediates the final proteolytic event in Alzheimer’s disease amyloid-bbiogenesis. This membrane complex of presenilin, ante-rior pharynx defective, nicastrin, and presenilin enhancer-2 cleaves the C-terminal 99-amino acid fragment of the amyloid precursor protein intra-membranously atc-sites to form C-terminally heterogeneous amyloid-b and cleaves at ane-site to release the intracellular domain or e-C-terminal fragment.