Evaluating the Presence of a Physiologic Ceiling in Amyloid Trajectories: Insights from the Sampled Iterative Local Approximation (SILA) Algorithm and Simulations

Amyloid trajectories in ADNI aligned based on SILA-estimated age of amyloid-positivity onset suggest an apparent lack of a physiologic ceiling for amyloid. This result is in contrast to prior studies which argue for a ceiling based on differences in amyloid by clinical stage and baseline amyloid level. Additionally, generating data based on influential models of temporal AD biomarker evolution does not produce trajectories consistent with those observed in ADNI. Growing longitudinal data availability and new quantitative tools should allow us to formally evaluate prevailing models of AD biomarker evolution.