. BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics. Hum Mol Genet. 2001 Jun 1;10(12):1317-24. PubMed.

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  1. A major conclusion of this paper is not proven by the data presented. That conclusion is that BACE1 is the primary β-secretase of the brain. That conclusion was arrived at based on β-secretase activity in cultured brain cells and brain homogenates. However, each of those assays contained E64, a potent, cathepsin inhibitor. The results, thus, do not rule out cathepsins as having β-secretase activity.