Speaker
Description
Tauopathies are a class of neurodegenerative diseases, such as Alzheimer's disease, characterized by a progressive accumulation of toxic misfolded tau proteins in the brain \cite{1}. Model-based approaches have shown that this progression, or “staging," follows a tau-spread process along the brain's white matter connective network, dubbed the “structural connectome" (SC). The Network Transport Model (NTM) \cite{2} was developed to build upon simple diffusion based models of tau spread \cite{3, 4} and demonstrate how global patterns of tau spread emerge from microscopic tau dynamics on the SC. However, the NTM suffers from an exceedingly high computational cost and slow simulations, hindering studies relating tau dynamics to global tau progression.
To overcome this challenge we developed Tau-BNO \cite{5}, a neural operator based surrogate model that learns the behavior of the NTM. The rapid NTM simulations of tau spread allowed by Tau-BNO reveal insights into how microscopic tau dynamics modulate global progression of tau. Cellular tau uptake and release was shown to be a direct modulator of the timeline of disease progression, while directional bias in tau transport regulated disease staging. Tau aggregation was shown to sequester tau available to spread while increasing the global burden of toxic tau aggregates. Tau-BNO made it possible to study the effect of microscopic tau dynamics on global disease patterns, showcasing the value of deep learning in biological discovery.
Bibliography
@article{2,
title={Biophysically realistic network-level transport model of tau progression with exosome-mediated release and uptake processes},
author={Barron, Nuutti and Tora, Veronica and Cozzolino, Emilia and Bertsch, Michiel and Raj, Ashish},
journal={bioRxiv},
pages={2026--01},
year={2026},
publisher={Cold Spring Harbor Laboratory}
}
@misc{5,
title={Tau-BNO: Brain Neural Operator for Tau Transport Model},
author={Nuutti Barron and Heng Rao and Urmi Saha and Yu Gu and Zhenghao Liu and Ge Yu and Defu Yang and Ashish Raj and Minghan Chen},
year={2026},
eprint={2603.08108},
archivePrefix={arXiv},
primaryClass={cs.CE},
url={https://arxiv.org/abs/2603.08108},
}
@article{4,
title={Network diffusion modeling explains longitudinal tau PET data},
author={Sch{\"a}fer, Amelie and Mormino, Elizabeth C and Kuhl, Ellen},
journal={Frontiers in neuroscience},
volume={14},
pages={566876},
year={2020},
publisher={Frontiers Media SA}
}
@article{3,
title={A network diffusion model of disease progression in dementia},
author={Raj, Ashish and Kuceyeski, Amy and Weiner, Michael},
journal={Neuron},
volume={73},
number={6},
pages={1204--1215},
year={2012},
publisher={Elsevier}
}
@article{1,
title={Tau in Alzheimer disease and related tauopathies},
author={Iqbal, Khalid and Liu, Fei and Gong, C-X and Grundke-Iqbal, Inge},
journal={Current Alzheimer Research},
volume={7},
number={8},
pages={656--664},
year={2010},
publisher={Bentham Science Publishers}
}
