Monoclonal Antibodies for Treatment of Alzheimer Disease

Alzheimer disease (AD) is a neurodegenerative disorder leading to progressive, irreversible destruction of neurons and loss of cognitive function and memory. Over time, patients progress to severe dementia, loss of independence, and death. Extracellular deposits of amyloid beta, referred to as amyloid plaques, are considered a hallmark of the disease. Beta-amyloid monomers lead to formation of beta oligomers and fibrils, are deposited as plaques, and then interact with tau fibrils, leading to formation of neuro-fibrillatory tangles. These pathophysiological changes and clinical manifestations of AD are progressive and occur along a continuum, and accumulation of amyloid beta may begin 20 years or more before symptoms arise. Two monoclonal antibodies (aducanumab and lecanemab) have been approved by the U.S. Food and Drug Administration under accelerated approval based on the reduction in amyloid beta plaques. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.