This study evaluated a blood-based screening algorithm using plasma Aβ42/Aβ40 and %p-tau217 to enrich amyloid PET-positive participants for the AHEAD 3-45 trial of lecanemab in preclinical Alzheimer's disease, deployed prospectively via a Mixture of Experts prediction model.
Adding plasma Aβ42/Aβ40 and %p-tau217 to the screening workflow reduced amyloid PET ineligibility from 71% to 31%; latent class analysis distinguished low, intermediate, and high amyloid groups, with %p-tau217 best predicting high amyloid burden and Aβ42/Aβ40 more specific for the low amyloid group.
The algorithm was developed during initial screening (without blood biomarkers) and then deployed prospectively, introducing a sequential/adaptive design that may limit generalizability; the intermediate amyloid group remains a challenge for binary PET classification; results are specific to the AHEAD 3-45 trial population.
A two-step plasma biomarker screen (Aβ42/Aβ40 first, then %p-tau217) can cut unnecessary amyloid PET scans by more than half in preclinical AD trials, meaningfully reducing participant and site burden. Clinicians and trialists should consider integrating plasma biomarker pre-screening into recruitment workflows for similar prevention trials.
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