 The amyloid cascade hypothesis has been the primary focus of research into Alzheimer's disease for decades. Despite some initial successes, recent studies have shown that the amyloid cascade hypothesis may not be the only factor involved in the development of Alzheimer's disease. This review discusses the evolution of the amyloid cascade hypothesis and its implications for Alzheimer's diagnosis and treatment. It also examines the pitfalls, promises, and unanswered questions associated with current anti-amyloid therapies, as well as potential strategies to optimize AD prevention and treatment. This article was authored by Yun Jong, Watcher Chen, Ran Li, and others.