Alzheimer's disease (AD) is the primary cause of dementia in the elderly. It 
remains incurable and poses a huge socio-economic challenge for developed 
countries with an aging population. AD manifests by progressive decline in 
cognitive functions and alterations in behaviour, which are the result of the 
extensive degeneration of brain neurons. The AD pathogenic mechanism involves 
the accumulation of amyloid beta peptide (Aβ), an aggregating protein fragment 
that self-associates to form neurotoxic fibrils that trigger a cascade of 
cellular events leading to neuronal injury and death. Researchers from academia 
and the pharmaceutical industry have pursued a rational approach to AD drug 
discovery and targeted the amyloid cascade. Schemes have been devised to prevent 
the overproduction and accumulation of Aβ in the brain. The extensive efforts of 
the past 20 years have been translated into bringing new drugs to advanced 
clinical trials. The most progressed mechanism-based therapies to date consist 
of immunological interventions to clear Aβ oligomers, and pharmacological drugs 
to inhibit the secretase enzymes that produce Aβ, namely β-site amyloid 
precursor-cleaving enzyme (BACE) and γ-secretase. After giving an update on the 
development and current status of new AD therapeutics, this review will focus on 
BACE inhibitors and, in particular, will discuss the prospects of verubecestat 
(MK-8931), which has reached phase III clinical trials.