BACE1 as a Therapeutic Target in Alzheimer's Disease: Rationale and Current Status

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system that causes dementia in a large percentage of the aged population and for which there are only symptomatic treatments. Disease-modifying therapies that are currently being pursued are based on the amyloid cascade theory. This states that accumulation of amyloid β (Aβ) in the brain triggers a cascade of cellular events leading to neurodegeneration. Aβ, which is the major constituent of amyloid plaques, is a peptidic fragment derived from proteolytic processing of the amyloid precursor protein (APP) by sequential cleavages that involve β-site APP-cleaving enzyme 1 (BACE1) and γ-secretase. Targeting BACE1 is a..