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

Nelda Antonovaite; Lianne A. Hulshof; Christiaan F.M. Huffels; Elly M. Hol; Wytse J. Wadman; Davide Iannuzzi

doi:10.1016/j.jmbbm.2021.104697

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

Nelda Antonovaite^*, Lianne A. Hulshof, Christiaan F.M. Huffels, Elly M. Hol, Wytse J. Wadman, Davide Iannuzzi

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

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 Alzheimer's disease (AD), magnetic resonance elastography (MRE) studies have indicated viscoelastic differences in the brain tissue of AD patients and healthy controls. 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%).

Original language	English
Article number	104697
Journal	Journal of the Mechanical Behavior of Biomedical Materials
Volume	122
DOIs	https://doi.org/10.1016/j.jmbbm.2021.104697
Publication status	Published - Oct 2021

Bibliographical note

Funding Information:
The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Program (FP/2007?2013)/ERC grant agreement no. [615170] and the Alzheimer Society in the Netherlands (Alzheimer Nederland WE.03-2017-04). The authors further thank M. Marrese for fruitful discussions, E. Paardekam for manufacturing indentation probes, and T. Smit for providing brain tissue slices and support in the lab.

Funding Information:
The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Program (FP/2007–2013)/ERC grant agreement no. [615170] and the Alzheimer Society in the Netherlands (Alzheimer Nederland WE.03-2017-04). The authors further thank M. Marrese for fruitful discussions, E. Paardekam for manufacturing indentation probes, and T. Smit for providing brain tissue slices and support in the lab.

Publisher Copyright:
© 2021

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Funding

The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Program (FP/2007?2013)/ERC grant agreement no. [615170] and the Alzheimer Society in the Netherlands (Alzheimer Nederland WE.03-2017-04). The authors further thank M. Marrese for fruitful discussions, E. Paardekam for manufacturing indentation probes, and T. Smit for providing brain tissue slices and support in the lab. The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Program (FP/2007–2013)/ERC grant agreement no. [615170] and the Alzheimer Society in the Netherlands (Alzheimer Nederland WE.03-2017-04). The authors further thank M. Marrese for fruitful discussions, E. Paardekam for manufacturing indentation probes, and T. Smit for providing brain tissue slices and support in the lab.

Funders	Funder number
Seventh Framework Programme	615170, FP/2007–2013
European Research Council	WE.03-2017-04
Seventh Framework Programme

Keywords

Alzheimer's disease
Biomechanical testing
Brain mechanics
Viscoelasticity

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10.1016/j.jmbbm.2021.104697

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title = "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 Alzheimer's disease (AD), magnetic resonance elastography (MRE) studies have indicated viscoelastic differences in the brain tissue of AD patients and healthy controls. 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%).",

keywords = "Alzheimer's disease, Biomechanical testing, Brain mechanics, Viscoelasticity",

author = "Nelda Antonovaite and Hulshof, {Lianne A.} and Huffels, {Christiaan F.M.} and Hol, {Elly M.} and Wadman, {Wytse J.} and Davide Iannuzzi",

note = "Funding Information: The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Program (FP/2007?2013)/ERC grant agreement no. [615170] and the Alzheimer Society in the Netherlands (Alzheimer Nederland WE.03-2017-04). The authors further thank M. Marrese for fruitful discussions, E. Paardekam for manufacturing indentation probes, and T. Smit for providing brain tissue slices and support in the lab. Funding Information: The research leading to these results has received funding from the European Research Council under the European Union{\textquoteright}s Seventh Framework Program (FP/2007–2013)/ERC grant agreement no. [615170] and the Alzheimer Society in the Netherlands (Alzheimer Nederland WE.03-2017-04). The authors further thank M. Marrese for fruitful discussions, E. Paardekam for manufacturing indentation probes, and T. Smit for providing brain tissue slices and support in the lab. Publisher Copyright: {\textcopyright} 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

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doi = "10.1016/j.jmbbm.2021.104697",

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AU - Antonovaite, Nelda

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AU - Huffels, Christiaan F.M.

AU - Hol, Elly M.

AU - Wadman, Wytse J.

AU - Iannuzzi, Davide

N1 - Funding Information: The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Program (FP/2007?2013)/ERC grant agreement no. [615170] and the Alzheimer Society in the Netherlands (Alzheimer Nederland WE.03-2017-04). The authors further thank M. Marrese for fruitful discussions, E. Paardekam for manufacturing indentation probes, and T. Smit for providing brain tissue slices and support in the lab. Funding Information: The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Program (FP/2007–2013)/ERC grant agreement no. [615170] and the Alzheimer Society in the Netherlands (Alzheimer Nederland WE.03-2017-04). The authors further thank M. Marrese for fruitful discussions, E. Paardekam for manufacturing indentation probes, and T. Smit for providing brain tissue slices and support in the lab. Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/10

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N2 - 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 Alzheimer's disease (AD), magnetic resonance elastography (MRE) studies have indicated viscoelastic differences in the brain tissue of AD patients and healthy controls. 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%).

AB - 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 Alzheimer's disease (AD), magnetic resonance elastography (MRE) studies have indicated viscoelastic differences in the brain tissue of AD patients and healthy controls. 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%).

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

Abstract

Bibliographical note

Funding

Keywords

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