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A robust and interpretable machine learning approach using multimodal biological data to predict future pathological tau accumulation

Published version
Peer-reviewed

Type

Article

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Authors

Abstract

The early stages of Alzheimer‘s disease (AD) involve interactions between multiple pathophysiological processes. Although these processes are well studied, we still lack robust tools to predict individualised trajectories of disease progression. Here, we employ a robust and interpretable machine learning approach to combine multimodal biological data and predict future pathological tau accumulation. In particular, we use machine learning to quantify interactions between key pathological markers (-amyloid, medial temporal atrophy, tau and APOE 4) at mildly impaired and asymptomatic stages of AD. Using baseline non-tau markers we derive a prognostic index that: a) stratifies patients based on future pathological tau accumulation and b) predicts individualised regional future rate of tau accumulation, c) translates predictions from deep phenotyping patient cohorts to cognitively normal individuals. Our results propose a robust approach for fine scale stratification and prognostication with translation impact for clinical trial design targeting the earliest stages of AD.

Description

Keywords

Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Cognitive Dysfunction, Humans, Machine Learning, Magnetic Resonance Imaging, Positron-Emission Tomography, tau Proteins

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Nature Research
Sponsorship
Wellcome Trust (205067/Z/16/Z)
Biotechnology and Biological Sciences Research Council (BB/P021255/1)
Alan Turing Institute (EP/N510129/1)
Alan Turing Institute (SF\087)
Alan Turing Institute (Unknown)
Wellcome Trust (221633/Z/20/Z)
Alzheimer's Research UK (ARUK-EDoN2021-002)
Wellcome Trust (223131/Z/21/Z)
EPSRC (EP/T017961/1)
This work was supported by grants to: Z.K. from the Biotechnology and Biological Sciences Research Council (H012508 and BB/P021255/1), Alan Turing Institute (TU/B/000095), Wellcome Trust (205067/Z/16/Z, 221633/Z/20/Z), Royal Society (INF\R2\202107); Z.K. and W.J.J. from the Global Alliance; W.J.J. US National Institute on Aging (AG034570, AG062542, AG024904). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012).
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