Wang and coauthors evaluate the usefulness of [18F]-AV-1451 positron emission tomography imaging to stage Alzheimer disease (AD) and assess the associations among Aβ, tau, and volume loss. An imaging study was conducted, and a total of 59 participants who were cognitively normal or had AD dementia were included. They report that the use of [18F]-AV-1451 has a potential for staging of the preclinical and clinical phases of AD. Aβ interacts with hippocampal and cortical tauopathy to affect neurodegeneration. In the absence of Aβ, hippocampal tau deposition may be insufficient for the neurodegenerative process that leads to AD. Editorial perspective is provided by William Jagust, MD.