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Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
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Complex interplay between brain function and structure during cerebral amyloidosis in APP transgenic mouse strains
Joanes Grandjean1, Rebecca Derungs2, Luka Kulic2
1Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland.
Neuroimage
|April 2, 2016
Summary
Neuroimaging reveals strain-specific brain changes in Alzheimer's disease mouse models. Functional and structural alterations varied, not directly correlating with amyloid deposition, highlighting model-specific pathology.
Area of Science:
- Neuroscience
- Medical Imaging
- Genetics
Background:
- Alzheimer's disease (AD) is a leading neurodegenerative disorder in aging populations.
- Neuroimaging, particularly MRI, shows brain alterations in AD patients and at-risk individuals, but mechanisms remain unclear.
- Murine models offer insights into AD-related functional and structural brain changes.
Purpose of the Study:
- To investigate strain-specific functional and structural brain alterations in transgenic mouse models of Alzheimer's disease using multi-parametric MRI.
- To compare neuroimaging findings across different AD mouse models with varying amyloid pathology.
Main Methods:
- Applied multi-parametric MRI, including resting-state fMRI and diffusion tensor imaging, in three transgenic mouse lines (E22ΔAβ, PSAPP, ArcAβ).
- Assessed brain function and structure, comparing transgenic mice to wild-type littermates.
- Analyzed intracellular amyloid-β aggregates, parenchymal plaques, and cerebral amyloid angiopathy.
Main Results:
- E22ΔAβ mice showed no significant functional or structural changes.
- PSAPP mice exhibited mild functional changes and increased isocortical volume.
- ArcAβ mice displayed reduced functional connectivity and midbrain volume increases, irrespective of amyloid deposition patterns.
Conclusions:
- Functional and structural brain changes in AD mouse models are strain-specific.
- Observed alterations do not directly correlate with the extent or type of amyloid deposition.
- These findings emphasize the importance of model selection for studying AD mechanisms.
