In the current issue of Nature Medicine, Faghihi et al. report that a noncoding antisense RNA against β-secretase, also known as BACE1 (β-site amyloid precursor protein (APP)-cleaving enzyme), may contribute to pathogenesis of Alzheimer's disease. BACE1 is a vertebrate-specific enzyme, which, together with presenilin-dependent γ-secretase, cleaves APP to generate the neurotoxic amyloid-β peptide (Aβ).