Once upon a time, the Amyloid Cascade Hypothesis

Recent trials with monoclonal antibodies targeting amyloid-β (Aβ) in Alzheimer's disease (AD) have sparked a renewed interest in disease-modifying therapies. Despite their promise, these trials leave the issue open and posit some doubts about the validity of the Amyloid Cascade Hypothesis (ACH). While some scores of neurocognitive tests improved upon treatment, real-world clinical benefits were minimal. This Viewpoint discusses additional, often overlooked findings from these trials. We also emphasize the multifactorial nature of AD and the need for a broader research perspective beyond the simplistic disease model provided by the ACH.