From large cross-sectional studies of autopsy material, it seems as if a time course of Alzheimer's Disease, at least on average, can be mapped out: a pattern of hierarchical vulnerability for neuronal loss and neurofibrillary tangles beginning in medial temporal lobe structures proceeding through association areas. Plaques follow their own temporal course, with widespread cortical deposits occurring even early in a disease process. The whole process may well take twenty years, the first half of which may be without overt symptoms.

How can we link the critical observations performed at autopsy with the events that occur over the previous twenty years of Alzheimer's Disease? This is the problem posed to a group of our colleagues who are using state-of-the-art neural imaging methods in patients and in animal models to illuminate the natural history of the disease - in the living brain.