Mechanical alterations of the hippocampus in the APP/PS1 Alzheimer's disease mouse model

Abstract

There is increasing evidence of altered tissue mechanics in neurodegeneration. However, due to difficulties in mechanical testing procedures and the complexity of the brain, there is still little consensus on the role of mechanics in the onset and progression of neurodegenerative diseases. In the case of Alzheimers disease (AD), magnetic resonance elastography (MRE) studies have indicated viscoelastic differences in the brain tissue of AD and healthy patients. However, there is a lack of viscoelastic data from contact mechanical testing at higher spatial resolution. Therefore, we report viscoelastic maps of the hippocampus obtained by a dynamic indentation on brain slices from the APP/PS1 mouse model where individual brain regions are resolved. A comparison of viscoelastic parameters shows that regions in the hippocampus of the APP/PS1 mice are significantly stiffer than wild-type (WT) mice and have increased viscous dissipation. Furthermore, indentation mapping at the cellular scale directly on the plaques and their surroundings did not show local alterations in stiffness although overall mechanical heterogeneity of the tissue was high (SD~40%). Therefore, reported mechanical alterations at a tissue scale indicates global remodeling of the brain tissue structure.