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Published on: May 23, 2025
Quantitative evaluation of MRI and histological characteristics of the 5xFAD Alzheimer mouse brain
N G Spencer1, L R Bridges, K Elderfield
1Basic Medical Sciences, St. George's University, London, SW17 0RE, UK. nspencer@sgul.ac.uk
Abstract:
Assessment of β-amyloid (Aβ) plaque load in Alzheimer's disease by MRI would provide an important biomarker to monitor disease progression or treatment response. Alterations in tissue structure caused by the presence of Aβ may cause localised changes that can be detected by quantitative T₁ and T₂ relaxation time measurements averaged over larger areas of tissue than that of individual plaques. We constructed depth profiles of the T₁ and T₂ relaxation times of the cerebral cortex with subjacent white matter and hippocampus in six 5xFAD transgenic and six control mice at 11 months of age. We registered these profiles with corresponding profiles of three immunohistochemical markers: β-amyloid; neuron-specific nuclear protein (NeuN), a marker of neuronal cell load; and myelin basic protein (MBP), a marker of myelin load. We found lower T₁ in the 5xFAD transgenic mice compared to wild type control mice at all depths, with maximum sensitivity for detection at specific layers. T₁ negatively correlated with Aβ staining intensity in the 5xFAD mice which had no changes in NeuN and MBP staining compared to wild type mice. We postulate that these relaxation time changes are due to the presence of β-amyloid in the transgenic mice. It may be clinically feasible to develop a similar layered analysis protocol as a biomarker for Alzheimer's disease in humans.
Insights
Quantitative MRI T1 relaxation time measurements can detect beta-amyloid plaque load in Alzheimer's disease models. This MRI biomarker may help monitor disease progression and treatment response in humans.
Area of Science:
- Neuroimaging
- Biomarkers
- Alzheimer's Disease Research
Background:
- Alzheimer's disease (AD) is characterized by beta-amyloid (Aβ) plaques.
- Assessing Aβ plaque load with MRI could offer a valuable biomarker for disease monitoring.
- Quantitative T₁ and T₂ relaxation times may detect tissue alterations caused by Aβ.
Purpose of the Study:
- To investigate the utility of quantitative T₁ and T₂ relaxation times as biomarkers for Aβ plaque load in a mouse model of Alzheimer's disease.
- To correlate MRI relaxation times with immunohistochemical markers of Aβ, neurons, and myelin.
- To assess the potential clinical feasibility of layered MRI analysis for AD diagnosis.
Main Methods:
- Depth profiles of T₁ and T₂ relaxation times were measured in the cerebral cortex and hippocampus of 5xFAD transgenic and wild-type mice.
- MRI data were registered with immunohistochemical staining for Aβ, NeuN (neuronal marker), and MBP (myelin marker).
- Correlation analyses were performed between relaxation times and marker staining intensities.
Main Results:
- Lower T₁ relaxation times were observed in 5xFAD mice compared to controls across all measured depths.
- T₁ relaxation time showed a negative correlation with Aβ staining intensity in 5xFAD mice.
- No significant differences in NeuN or MBP staining were found between 5xFAD and control mice, suggesting Aβ is the primary driver of T₁ changes.
Conclusions:
- Quantitative T₁ MRI relaxation time measurements are sensitive to Aβ plaque load in the 5xFAD mouse model.
- T₁ relaxation time changes are likely attributable to the presence of Aβ, independent of neuronal or myelin alterations.
- Layered MRI analysis holds promise as a non-invasive biomarker for Alzheimer's disease in humans.