Linking amyloid to clinical outcome: A quantitative semi‐mechanistic model based on the A/T/N biomarker framework to simulate the natural history of Alzheimer’s disease and the effects of anti‐amyloid treatment

According to FDA’s literature review of clinical trial data from a number of anti‐amyloid antibodies, a “clear relationship” was demonstrated between the extent of amyloid plaque removal measured by amyloid PET and the magnitude of clinical benefit measured by the placebo‐corrected difference in the CDR sum of boxes (CDR‐SB). To understand this relationship from a theoretical perspective we developed a quantitative semi‐mechanistic representation of the A (amyloid)/T (tau)/N (neurodegeneration) framework (the Q‐ATN model) in order to simulate the natural history of disease progression and the effects of anti‐amyloid therapy.