The Alzheimer community was recently confronted with sobering news: a phase III trial of aducanumab, an anti-amyloid compound that represented the most recent hope for a disease-modifying therapy (DMT), was discontinued when a futility analysis determined that no significant likelihood of therapeutic efficacy existed. This was a disheartening outcome, given promising phase Ib data that showed dose-dependent disease slowing and plaque clearance.¹ Thus, the world is still facing an Alzheimer disease (AD) epidemic without any DMTs to combat the staggering financial and human costs.² Symptomatic treatments (eg, cholinesterase inhibitors) that temporarily slow decline are available, but these do not modify disease progression. Earlier hope of addressing AD neuropathology by reducing buildup or enhancing removal of β-amyloid (Aβ) plaques has been moderated by the failure of more than a dozen anti-amyloid compounds. In this Viewpoint, we explore potential reasons for these failures, describe the response of the AD community, and highlight reasons for continued optimism.

阿尔茨海默氏症社区最近面临着一个严峻的消息：当无效性分析确定没有显着可能性的抗坏血酸疗法（DMT）时，阿杜那单抗（一种代表最新的疾病缓解疗法（DMT）的抗淀粉样蛋白化合物）的III期临床试验就中止了。存在治疗功效。鉴于有希望的Ib期数据显示剂量依赖性疾病放慢和斑块清除，这是令人沮丧的结果。¹因此，世界上仍然面临着阿尔茨海默氏病（AD）的流行，而没有任何DMT来应对惊人的财务和人力成本。^2个有症状的治疗方法（例如，胆碱酯酶抑制剂）可以暂时延缓衰老，但这些方法不会改变疾病的进展。通过减少十二种抗淀粉样蛋白化合物的失败，减轻了通过减少β淀粉样蛋白（Aβ）斑块的形成或增强清除AD神经病理学的希望。在此观点中，我们探讨了导致这些失败的潜在原因，描述了AD社区的反应，并强调了持续乐观的原因。