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More efficient screening for preclinical Alzheimer's clinical trials using mixture of experts.

Created on 09 Sep 2026

Authors

Oliver Langford, Rema Raman, Paul Aisen, Reisa Sperling, Keith Johnson, Doris Molina-Henry, Pallavi Sachdev, David Li, Gustavo A Jimenez-Maggiora, Sterling C Johnson, Joel B Braunstein, Colin Birkenbihl, Madison Cuppels, Rachel F Buckley, Robert A Rissman, Michael C Donohue

Published in

Alzheimer's & dementia : the journal of the Alzheimer's Association. Volume 22. Issue 9. Pages e71681.

Abstract

Blood plasma biomarkers identifying Alzheimer's disease (AD) neuropathology offer accessible and scalable alternatives to lumbar puncture and positron emission tomography (PET) scans, with potential efficiency gains in clinical trial recruitment.
We evaluated the impact of a blood-based screening algorithm on recruitment for the AHEAD 3-45 trial testing lecanemab in preclinical AD. The algorithm was developed during initial screening without blood plasma and subsequently deployed using a Mixture of Experts prediction model to estimate amyloid PET positivity; analyses reflect prospective enrichment and model characterization.
The algorithm incorporating amyloid beta A β 42 / A β 40 and subsequently adding percent phosphorylated tau 217 (%p-tau217), reduced ineligibility on amyloid PET from 71% to 31%. Latent class analysis identified low, intermediate, and high amyloid groups. Model-based analyses indicated %p-tau217 predicts High amyloid group, whereas A β 42 / A β 40 was more specific for the low group.
Blood plasma screening reduced participant and site burden, while preserving enrichment for amyloid positivity for a preclinical AD trial.

PMID:
42713877
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.

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