Amyloid plaques, which are composed of amyloid-beta peptide (Abeta), signify Alzheimer's disease pathology. Secretases generate Abeta by processing the beta-amyloid precursor protein. gamma-Secretase, a complex comprising four different proteins, liberates Abeta from its precursor by intramembrane proteolysis. The first impression of the shape of gamma-secretase has recently been revealed by electron microscopy. It indicates a spherical transmembrane particle with an interior chamber that, presumably, accommodates its catalytic residues, and two openings that might be exit sites for the cleavage products.