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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.<\/jats:p>","DOI":"10.64898\/2026.06.02.729568","type":"posted-content","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T20:25:11Z","timestamp":1780691111000},"source":"Crossref","is-referenced-by-count":0,"title":["Spatially resolved mapping of tau amplification rates via differentiable simulation of prion-like propagation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2801-4522","authenticated-orcid":false,"given":"Yohei","family":"Kondo","sequence":"first","affiliation":[{"name":"Center for One Medicine Innovative Translational Research (COMIT), Nagoya University, Nagoya, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honda","family":"Naoki","sequence":"additional","affiliation":[{"name":"Center for One Medicine Innovative Translational Research (COMIT), Nagoya University, Nagoya, 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