Høilund-Carlsen and colleagues raise concern regarding the reliability of amyloid PET to exclude Alzheimer disease. We present additional studies of amyloid PET and discuss the diagnostic challenges in Alzheimer disease. We discuss the limitations of amyloid in diagnosis and evaluation of therapy response in AD.

Høilund-Carlsen and colleagues raise important issues related to amyloid PET, diagnosis of Alzheimer disease, and recently approved antiamyloid treatment aducanumab. We discuss new developments that may direct us to methods of presymptomatic detection of Alzheimer disease and development of effective prevention and therapy.