BACE inhibitors in clinical development for the treatment of Alzheimer’s disease

ABSTRACTIntroduction: The amyloid hypothesis of Alzheimer’s disease (AD) affirms that brain accumulation of amyloid-β (Aβ) oligomers and soluble aggregates represent the major pathological event of the disease. Several anti-Aβ small organic molecules, monoclonal antibodies and antigens were developed to interfere with Aβ production and clearance, including β–site amyloid precursor protein cleaving enzyme (BACE) inhibitors, blocking the first enzymatic step of Aβ formation. All these approaches, including BACE inhibitors, have failed in large randomized clinical trials (RCTs) in mild-to-moderate AD, but further studies are now being carried out in patients at early AD stages and in asymptomatic subjects at risk of developing AD.Areas covered: The paper provides a comprehensive review of BACE inhibitors for AD treatment, focusing on the most advanced compounds in Phase III RCTs.Expert commentary: BACE inhibitors inhibited robustly, and dose-dependently, Aβ formation in cerebrospinal fluid of AD patients, bu...