Spatially resolved mapping of tau amplification rates via differentiable simulation of prion-like propagation
Kondo, Y.; Naoki, H.
Show 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 whole-brain scale. Here we present a differentiable reaction-diffusion framework that enables inference of spatially resolved tau amplification rates directly from tau PET data. By integrating MRI-informed forward simulation with error backpropagation, our approach reconstructs voxel-wise propagation kinetics across the human brain. The inferred maps revealed structured, non-uniform patterns of tau amplification, with both cross-individual consistency and substantial inter-individual variability. These patterns were distinct from observed tau burden, revealing regional vulnerability that is not apparent from static tau PET maps alone. Integration with transcriptomic data identifies 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.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- AI-driven fusion of neurological work-up for assessment of biological Alzheimer’s disease 96%
- Characterizing spatiotemporal white matter hyperintensity pathophysiology in vivo to disentangle vascular and neurodegenerative contributions 95%
- A hierarchical atlas of the human cerebellum for functional precision mapping 94%
Similar papers in this journal
- Diffusion time-related structure-function coupling reveals differential association with inter-individual variations in body mass index 94%
- Individualized event structure drives individual differences in whole-brain functional connectivity 94%
- Multi-modal Latent Factor Exploration of Atrophy, Cognitive and Tau Heterogeneity in Alzheimer’s Disease 93%
Similar papers in this journal
- High-order functional interactions in ageing explained via alterations in the connectome in a whole-brain model 92%
- Multidimensional analysis and detection of informative features in diffusion MRI measurements of human white matter 92%
- Searching through functional space reveals distributed visual, auditory, and semantic coding in the human brain 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.