Exploring tau protein and amyloid-beta propagation: a sensitivity analysis of mathematical models based on biological data

TL;DR

This paper investigates how the equilibrium concentrations of tau and amyloid-beta proteins influence their propagation patterns in Alzheimer's disease using mathematical models and advanced numerical methods on patient-specific brain geometries.

Contribution

It performs a sensitivity analysis of heterodimer and Fisher-Kolmogorov models to assess the impact of protein concentration on spreading patterns, calibrated with biological data.

Findings

Sensitivity of models to protein concentration equilibrium values.

Advanced numerical methods improve front propagation accuracy.

Discussion on model applicability for protein spread simulation.

Abstract

Alzheimer's disease is the most common dementia worldwide. Its pathological development is well known to be connected with the accumulation of two toxic proteins: tau protein and amyloid-$\beta$. Mathematical models and numerical simulations can predict the spreading patterns of misfolded proteins in this context. However, the calibration of the model parameters plays a crucial role in the final solution. In this work, we perform a sensitivity analysis of heterodimer and Fisher-Kolmogorov models to evaluate the impact of the equilibrium values of protein concentration on the solution patterns. We adopt advanced numerical methods such as the IMEX-DG method to accurately describe the propagating fronts in the propagation phenomena in a polygonal mesh of sagittal patient-specific brain geometry derived from magnetic resonance images. We calibrate the model parameters using biological measurements in the brain cortex for the tau protein and the amyloid-$\beta$ in Alzheimer's patients and controls. Finally, using the sensitivity analysis results, we discuss the applicability of both models in the correct simulation of the spreading of the two proteins.