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Alzheimer's & dementia : the journal of the Alzheimer's Association
Published

Machine learning prediction of tau-PET in Alzheimer's disease using plasma, MRI, and clinical data

Authors

Linda Karlsson, Jacob Vogel, Ida Arvidsson, Kalle Åström, Olof Strandberg, Jakob Seidlitz, Richard A I Bethlehem, Erik Stomrud, Rik Ossenkoppele, Nicholas J Ashton, Henrik Zetterberg, Kaj Blennow, Sebastian Palmqvist, Ruben Smith, Shorena Janelidze, Renaud La Joie, Gil D Rabinovici, Alexa Pichet Binette, Niklas Mattsson-Carlgren, Oskar Hansson

Abstract

Alzheimers Dement. 2025 Feb;21(2):e14600. doi: 10.1002/alz.14600.

ABSTRACT

INTRODUCTION: Tau positron emission tomography (PET) is a reliable neuroimaging technique for assessing regional load of tau pathology in the brain, but its routine clinical use is limited by cost and accessibility barriers.

METHODS: We thoroughly investigated the ability of various machine learning models to predict clinically useful tau-PET composites (load and laterality index) from low-cost and non-invasive features, for example, clinical variables, plasma biomarkers, and structural magnetic resonance imaging (MRI).

RESULTS: Models including plasma biomarkers yielded the most accurate predictions of tau-PET burden (best model: R-squared = 0.66-0.69), with especially high contribution from plasma phosphorylated tau-217 (p-tau217). MRI variables were the best predictors of asymmetric tau load between the two hemispheres (best model: R-squared = 0.28-0.42). The models showed high generalizability to external test cohorts with data collected at multiple sites. Through a proof-of-concept two-step classification workflow, we also demonstrated possible model translations to a clinical setting.

DISCUSSION: This study highlights the promising and limiting aspects of using machine learning to predict tau-PET from scalable cost-effective variables, with findings relevant for clinical settings and future research.

HIGHLIGHTS: Accessible variables showed potential in estimating tau tangle load and distribution. Plasma phosphorylated tau-217 (p-tau217) and magnetic resonance imaging (MRI) were the best predictors of different tau-PET (positron emission tomography) composites. Machine learning models demonstrated high generalizability across AD cohorts.

PMID:39985487 | DOI:10.1002/alz.14600

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg