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β-Site APP-cleaving enzyme 1 (BACE1) inhibition to treat Alzheimer’s disease also inhibits BACE2. This work shows BACE2 expression in the mouse brain and identifies its substrates. Increased BACE2 processing of vascular cell adhesion molecule 1 during inflammatory conditions cautions the use of current nonspecific BACE1 inhibitors in the clinic.

BACE2 distribution in major brain cell types and identification of novel substrates