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Updated: May 9, 2026
Full- versus Sub-Regional Quantification of Amyloid-Beta Load on Mouse Brain Sections
Published on: May 19, 2022
Longitudinal Assessment of Amyloid Pathology in Transgenic ArcAβ Mice Using Multi-Parametric Magnetic Resonance
Jan Klohs1, Igna Wojtyna Politano, Andreas Deistung
1Institute for Biomedical Engineering, ETH and University of Zurich, Zurich, Switzerland ; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
Abstract:
Magnetic resonance imaging (MRI) can be used to monitor pathological changes in Alzheimer's disease (AD). The objective of this longitudinal study was to assess the effects of progressive amyloid-related pathology on multiple MRI parameters in transgenic arcAβ mice, a mouse model of cerebral amyloidosis. Diffusion-weighted imaging (DWI), T1-mapping and quantitative susceptibility mapping (QSM), a novel MRI based technique, were applied to monitor structural alterations and changes in tissue composition imposed by the pathology over time. Vascular function and integrity was studied by assessing blood-brain barrier integrity with dynamic contrast-enhanced MRI and cerebral microbleed (CMB) load with susceptibility weighted imaging and QSM. A linear mixed effects model was built for each MRI parameter to incorporate effects within and between groups (i.e. genotype) and to account for changes unrelated to the disease pathology. Linear mixed effects modelling revealed a strong association of all investigated MRI parameters with age. DWI and QSM in addition revealed differences between arcAβ and wt mice over time. CMBs became apparent in arcAβ mice with 9 month of age; and the CMB load reflected disease stage. This study demonstrates the benefits of linear mixed effects modelling of longitudinal imaging data. Moreover, the diagnostic utility of QSM and assessment of CMB load should be exploited further in studies of AD.
Insights
This study used advanced MRI techniques to track Alzheimer's disease (AD) progression in mice. Quantitative susceptibility mapping (QSM) and cerebral microbleed (CMB) detection showed promise for monitoring AD-related brain changes over time.
Area of Science:
- Neuroimaging
- Biomedical Engineering
- Alzheimer's Disease Research
Background:
- Alzheimer's disease (AD) is characterized by progressive neurodegeneration and amyloid pathology.
- Magnetic resonance imaging (MRI) offers non-invasive methods to monitor pathological changes in the brain.
- Transgenic mouse models are crucial for understanding AD pathogenesis and testing interventions.
Purpose of the Study:
- To assess the impact of amyloid-related pathology on multiple MRI parameters in transgenic arcAβ mice.
- To longitudinally evaluate structural alterations and tissue composition changes over time using advanced MRI techniques.
- To investigate vascular function and integrity, including blood-brain barrier integrity and cerebral microbleed (CMB) load.
Main Methods:
- Longitudinal study design in transgenic arcAβ mice and wild-type (wt) littermates.
- Application of Diffusion-Weighted Imaging (DWI), T1-mapping, and Quantitative Susceptibility Mapping (QSM).
- Assessment of vascular parameters using dynamic contrast-enhanced MRI and susceptibility weighted imaging for CMB detection.
- Statistical analysis using linear mixed effects modeling to account for age and genotype effects.
Main Results:
- All investigated MRI parameters showed a strong association with age.
- Diffusion-Weighted Imaging (DWI) and Quantitative Susceptibility Mapping (QSM) revealed significant differences between arcAβ and wt mice over time.
- Cerebral microbleeds (CMBs) became apparent in arcAβ mice around 9 months of age, with CMB load correlating with disease stage.
Conclusions:
- Linear mixed effects modeling is beneficial for analyzing longitudinal imaging data in AD mouse models.
- Quantitative Susceptibility Mapping (QSM) and cerebral microbleed (CMB) assessment demonstrate diagnostic utility for monitoring Alzheimer's disease.
- These advanced MRI techniques hold potential for future AD research and therapeutic development.