Towards the Biomechanics of Alzheimer’s Disease: Computational Models

Abstract

AbstractBackgroundPhysical changes in the brain microenvironment are highly associated with changes in mechanosensitivity of neuronal cells and mechanical properties of brain tissue. The progression of amyloid plaques and neurofibrillary tangles in the brain network significantly affects brain microstructure in Alzheimer’s disease (AD). To better understand the underlying mechanisms of AD, it is crucial to explore the effect of neuropathologies that cause brain tissue softening.MethodWe propose a microstructural model of brain white matter characterized by axons embedded in an extracellular matrix (ECM). The microscale is described by a representative volume element and includes features such as mechanical properties of axons and ECM, distribution of axon diameters, and axon tortuosity from experimental observations. The aim of this work is to investigate how the presence of β‐amyloid as hard senile plaques in the ECM and neurofibrillary tangles leads to softer mechanical properties of the brain during AD. The model is validated by simulating healthy brain tissue and comparing the homogenized response with existing experimental data.ResultPreliminary analyses to validate the model have shown tissue behavior similar to that seen in the mechanical experiments. In the case of AD, as expected, changes in the mechanical properties of the ECM due to the presence of hard senile plaques, demyelination due to the detachment of hyperphosphorylated tau proteins and neuronal death significantly affect the material properties at the macroscale.ConclusionThe combination of computational mechanical models with experimental observations opens a window to assess the structure‐function relationship of brain tissues in neuropathological disorders, which may be particularly useful to precisely design biomarkers for early detection or more informed therapeutic strategies.References• Schäfer, J. Weickenmeier, and E. Kuhl, “The interplay of biochemical and biomechanical degeneration in Alzheimer’s disease”, Comput. Methods Appl. Mech. Eng., vol. 352, pp. 369‐388, 2019.• M. Hall, E. Moeendarbary, and G.K. Sheridan, “Mechanobiology of the brain in ageing and Alzheimer’s disease”, Eur. J. Neurosci., pp. 1‐28, 2020.• Budday, G. Sommer, C. Birkl, C. Langkammer, J. Haybaeck, J. Kohnert, M. Bauer, F. Paulsen, P. Steinmann, E. Kuhl, G.A. Holzapfel, “Mechanical characterization of human brain tissue”, Acta Biomater., pp. 319‐340, 2017.