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Accumulation of the amyloid-β peptide (αβ) in the cerebral cortex is a critical event in the pathogenesis of Alzheimer's disease. The b-amyloid protein precursor (APP) is cleaved by β-secretase, producing a soluble derivative of the protein and a membrane anchored 99-amino acid carboxy-terminal fragment (C99). The C99 fragment serves as substrate for g-secretase to generate the 4 kDa amyloid-b peptide (αβ), which is deposited in the brains of all suffers of Alzheimer's disease.