Researchers at Amgen (Thousand Oak, CA) have cloned and characterized a β-secretase that could represent a potential target for Alzheimer's therapies ( Science 286, 735–741, 1999). Secretases are involved in the processing of amyloid precursor protein (APP) to produce amyloid β, which accumulates to form plaques. Until recently, many researchers had been attempting to find the secretase (termed BACE for beta-site APP-cleaving enzyme) using biochemical purification. In contrast, the Amgen team, headed by Martin Citron, used an expression cloning strategy to identify the protein. Overexpression of the BACE was shown to increase the amount of APP cleavage products in a manner consistent with β-secretase action. Antisense inhibition of BACE also decreased the amount of APP cleavage products in cell culture. Using cellular immunostaining and ELISA quantification, the researchers confirmed that the subcellular location and expression pattern of BACE corresponded with those predicted for β-secretase. According to Amgen, screening is already under way to identify a small molecule inhibitor of the protein. Meanwhile, Bart De Strooper and colleagues have used confocal microscopy to show (J. Cell. Biol. 147, 277—294, 1999) that presenilin-1 and APP are located in the same places, adding to weight to the evidence that this protein might be the elusive cellular γ-secretase that prevents amyloid β formation.