Recent advances in molecular imaging using positron emission tomography have permitted the 4-dimensional mapping of Alzheimer’s disease related pathology. The two aggregated proteins, beta-amyloid and tau, can now be visualized, along with the presumptive consequences of their deposition – brain degeneration and cognitive decline. This talk will review both cross sectional and longitudinal data concerning how tau and amyloid interact, and how they are related to neurodegeneration and cognition. The framework for discussion is a sequential model of biomarker changes. The question of whether and how well the observed data fit this model will be discussed.