Spatially resolved mapping of tau amplification rates via differentiable simulation of prion-like propagation

Kondo, Y.; Naoki, H.

doi:10.64898/2026.06.02.729568

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bioRxiv · 10.64898/2026.06.02.729568

Spatially resolved mapping of tau amplification rates via differentiable simulation of prion-like propagation

Kondo, Y.·Naoki, H.

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Abstract

Neurodegenerative diseases exhibit characteristic yet heterogeneous patterns of pathological spread, whose underlying determinants remain unclear. A central challenge is that inferring spatially heterogeneous propagation kinetics from neuroimaging data constitutes a high-dimensional inverse problem that has remained intractable at the whole-brain scale. Here, we present a differentiable reaction-diffusion framework that enables inference of spatially resolved tau amplification rates from tau PET data. By integrating MRI-informed forward simulation with error backpropagation, our approach reconstructs subject-specific voxel-wise maps of tau amplification rates across the human brain. Analysis of the inferred maps showed that the amplification rates have a positive spatial association with amyloid PET, suggesting that they capture aspects of regional vulnerability to amyloid-driven tau accumulation. Furthermore, integration with transcriptomic data identified gene expression programs associated with regional variation in amplification. These findings provide a data-driven framework linking molecular architecture to large-scale propagation dynamics in neurodegeneration.

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Kondo, Y., Naoki, H.. 2026-06-05. Spatially resolved mapping of tau amplification rates via differentiable simulation of prion-like propagation. https://doi.org/10.64898/2026.06.02.729568

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