The FDA approved aducanumab, an anti-amyloid antibody, for Alzheimer's disease (AD) in 2021 under an accelerated approval pathway, sparking hope for a disease-modifying therapy. However, two years later, aducanumab failed to launch, highlighting the complexities of dementia and the need for thorough, transparent drug approval processes. The approval was controversial, with concerns over its efficacy, safety, and the role of regulatory agencies. Key lessons from aducanumab's failure include the limitations of antiamyloid strategies in a complex disease, the need for diverse clinical trials, the risks of futility analyses, and the importance of transparency in the approval process. The failure also underscores the dementia field's unpreparedness to transition from controlled clinical trials to real-world use of resource-intensive therapies. Aducanumab's approval was based on a surrogate endpoint (reduction of amyloid plaques via PET), requiring a confirmatory trial. Despite initial optimism, aducanumab showed only minor slowing of disease progression, with significant side effects like ARIA. The approval process was criticized for lacking transparency and for not adequately considering clinical relevance. The failure of aducanumab has prompted calls for regulatory reforms, including more rigorous trial designs, diverse participant enrollment, and improved communication between stakeholders. The story emphasizes the need for effective, equitable, and transparent approaches to dementia research and treatment.The FDA approved aducanumab, an anti-amyloid antibody, for Alzheimer's disease (AD) in 2021 under an accelerated approval pathway, sparking hope for a disease-modifying therapy. However, two years later, aducanumab failed to launch, highlighting the complexities of dementia and the need for thorough, transparent drug approval processes. The approval was controversial, with concerns over its efficacy, safety, and the role of regulatory agencies. Key lessons from aducanumab's failure include the limitations of antiamyloid strategies in a complex disease, the need for diverse clinical trials, the risks of futility analyses, and the importance of transparency in the approval process. The failure also underscores the dementia field's unpreparedness to transition from controlled clinical trials to real-world use of resource-intensive therapies. Aducanumab's approval was based on a surrogate endpoint (reduction of amyloid plaques via PET), requiring a confirmatory trial. Despite initial optimism, aducanumab showed only minor slowing of disease progression, with significant side effects like ARIA. The approval process was criticized for lacking transparency and for not adequately considering clinical relevance. The failure of aducanumab has prompted calls for regulatory reforms, including more rigorous trial designs, diverse participant enrollment, and improved communication between stakeholders. The story emphasizes the need for effective, equitable, and transparent approaches to dementia research and treatment.