The present invention provides the enzyme and enzymatic procedures for cleaving the .beta. secretase cleavage site of the APP protein and associated nucleic acids, peptides, vectors, cells and cell isolates and assays. An enzyme that cleaves the .alpha.-secretase site of APP also is provided. The invention further provides a modified APP protein and associated nucleic acids, peptides, vectors, cells, and cell isolates, and assays that are particularly useful for identifying candidate therapeutics for treatment or prevention of Alzheimer's disease.