Nonlocal Models in the Analysis of Brain Neurodegenerative Protein Dynamics with Application to Alzheimer's Disease

TL;DR

This paper introduces a multiscale nonlocal model to analyze the propagation of toxic proteins in the brain, providing insights into Alzheimer's disease progression and regional damage patterns.

Contribution

It develops a novel nonlocal, multiscale model incorporating brain connectome data to study toxic protein spread in Alzheimer's disease.

Findings

Spreading patterns are similar across the brain but concentrations vary regionally.

Propagation time differs across brain regions.

The model's stability analysis confirms the robustness of stationary states.

Abstract

It is well known that today nearly one in six of the world's population has to deal with neurodegenerative disorders. While a number of medical devices have been developed for the detection, prevention, and treatments of such disorders, some fundamentals of the progression of associated diseases are in urgent need of further clarification. In this paper, we focus on Alzheimer's disease, where it is believed that the concentration changes in amyloid-beta and tau proteins play a central role in its onset and development. A multiscale model is proposed to analyze the propagation of these concentrations in the brain connectome. In particular, we consider a modified heterodimer model for the protein-protein interactions. Higher toxic concentrations of amyloid-beta and tau proteins destroy the brain cell. We have studied these propagations for the primary and secondary and their mixed tauopathy. We model the damage of a brain cell by the nonlocal contributions of these toxic loads present in the brain cells. With the help of rigorous analysis, we check the stability behaviour of the stationary points corresponding to the homogeneous system. After integrating the brain connectome data into the developed model, we see that the spreading patterns of the toxic concentrations for the whole brain are the same, but their concentrations are different in different regions. Also, the time to propagate the damage in each region of the brain connectome is different.