Alzheimer’s disease unfolds over many years through a complex interplay of amyloid, tau, genetics, lipid biology, and the brain’s immune response. John Hardy, Ph.D., explains how rare inherited forms of Alzheimer’s disease helped shape current thinking about how the disease begins, then connects those discoveries to broader questions about late onset disease and why it develops differently across people. Hardy shows that amyloid and tau are linked but not identical, and argues that problems with protein buildup and clearance both matter in understanding the disease. He also emphasizes that Alzheimer’s is not a single event but a long process, which makes prediction, diagnosis, and treatment especially difficult. While current amyloid-targeting therapies can help and show measurable benefit, Hardy says they do not stop the disease, underscoring the need for earlier diagnosis, better treatments, and wider access to care Series: "Shiley Endowed Lecture" [Health and Medicine] [Show ID: 41250]