Immunotherapies for Alzheimer's disease

Antibodies targeting amyloid-β aggregates slow decline in Alzheimer’s disease Three monoclonal antibodies—aducanumab, lecanemab, and donanemab— that target amyloid-β (Aβ) deposits in the brain slow cognitive and functional decline in early Alzheimer’s disease (AD) ( 1 – 3 ). The data from the phase 3 clinical trials in mildly symptomatic individuals with AD demonstrate that Aβ reduction has modest clinical benefit. This supports the central tenet of the amyloid cascade hypothesis (ACH), which proposes that Aβ deposits play a causal, initiating role in AD. However, they also show that targeting Aβ deposits in the symptomatic stage of the disease is not a panacea—a finding that is nevertheless consistent with the presumed initiating role of Aβ aggregation in AD pathogenesis. Further, the studies highlight the pivotal role for imaging and fluid biomarkers in developing disease-modifying therapies (DMTs) for AD. Unanswered questions, including those around differences between the treatments, long-term benefits, and the risk-benefit ratio in real-world populations, remain.