BACE1 inhibitor reduces β-amyloid production in humans

Inhibition of aspartyl protease β-site amyloid precursor protein cleaving enzyme 1 (BACE1), required for production of β-amyloid (Aβ) peptides, is an attractive approach to lower Aβ levels in AD. Kennedy et al. present verubecestat (MK-8931), the first BACE1 inhibitor to reach phase III clinical trials. Orally administered verubecestat safely reduced plasma, cerebrospinal fluid (CSF), and cortical Aβ₄₀, Aβ₄₂ and soluble amyloid precursor protein-β (sAPPβ) production in rats and monkeys. In both healthy human subjects and patients with AD, verubecestat reduced Aβ₄₀, Aβ₄₂ and sAPPβ in the CSF and was well-tolerated.