Aducanumab (Aduhelm) for Alzheimer's Disease
Also known as: Aduhelm, BIIB037
The first anti-amyloid antibody approved for Alzheimer's, aducanumab generated intense debate about the amyloid hypothesis and clinical trial design.
Mechanism of Action
Aducanumab is a human IgG1 monoclonal antibody that selectively binds aggregated forms of amyloid-beta (oligomers and fibrils). It promotes microglial phagocytic clearance of amyloid plaques through Fc receptor engagement. PET imaging confirmed dose-dependent plaque reduction.
General mechanism: Anti-amyloid-beta monoclonal antibody targeting aggregated Aβ forms. Promotes microglial phagocytic plaque clearance.
Current Evidence
EMERGE trial reported clinical outcomes; ENGAGE trial did not replicate these findings. Controversial accelerated FDA approval (2021) based on amyloid reduction as surrogate endpoint. Subsequently superseded by lecanemab and donanemab in the literature. Withdrawn from US market (2024).
Clinical Status: FDA accelerated approval (2021), subsequently withdrawn (2024). Superseded by lecanemab and donanemab.
Safety Profile
ARIA (amyloid-related imaging abnormalities) — edema and microhemorrhages — in 35-40% of patients. Higher risk in APOE4 carriers. Regular MRI monitoring required.
Key Research Questions
- What lessons from aducanumab's clinical program inform next-generation anti-amyloid strategies?
- Is there a subpopulation that clearly benefits from aggressive plaque clearance?
- How do ARIA risk profiles compare between anti-amyloid antibodies?