A Region-Calibrated Spatiotemporal Model of Post-Traumatic Tau Aggregation Coupled to a Translational Mouse-to-Human Cortical Indentation Simulation

Traumatic brain injury (TBI) is increasingly recognized as a relevant initiating factor in tau-related neurodegenerative processes, yet the quantitative link between a controlled mechanical insult and the long-term spatiotemporal evolution of tau pathology remains insufficiently defined. In the present study, a translational computational framework is proposed to predict post-traumatic tau accumulation by combining region-specific Avrami-type nucleation-growth kinetics with a finite-element simulation of controlled cortical impact (CCI) at human scale. The temporal component of the model is calibrated independently for cortex, hippocampus, and brainstem using experimental post-TBI tau-burden measurements derived from a tau-transgenic mouse model of CCI. The formulation preserves anatomical specificity by calibrating each region independently. The biomechanical component is built around a localized indentation framework designed to mimic the experimental CCI configuration. To transfer the loading concept from mouse to human, the indenter geometry is scaled using cortical thickness as the primary characteristic length, ensuring that the local indentation problem remains mechanically interpretable across species. The resulting strain field is then normalized and used to distribute tau spatially within each region while preserving the calibrated regional mean kinetics. The proposed framework provides a region-aware and mechanically grounded route for studying how a controlled cortical insult may trigger heterogeneous tau accumulation over time, thereby offering a computational basis for investigating early mechanobiological pathways relevant to trauma-associated tauopathy and chronic traumatic encephalopathy (CTE).