Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging.

Area of Science:

• Neuroimaging
• Biomarker Development
• Alzheimer's Disease Research

Background:

• Alzheimer's disease pathogenesis involves progressive neurodegeneration.
• 5xFAD mouse models exhibit amyloid pathology relevant to Alzheimer's disease.
• Understanding age-dependent microstructural changes is crucial for preclinical research.

Purpose of the Study:

• To evaluate age-dependent microstructure alterations in 5xFAD mice.
• To assess the utility of high-resolution diffusion tensor imaging (DTI) in detecting these changes.
• To investigate DTI metrics, specifically fractional anisotropy (FA) and mean diffusivity (MD), as potential biomarkers.

Main Methods:

• High-resolution 9.4T DTI scans were performed on 5xFAD mice at 4, 7.5, and 12 months, and wild-type controls at 4 months.
• Isotropic spatial resolution of 100 μm was achieved using a 3D echo-planar imaging (EPI) sequence.
• DTI metrics (FA, MD) were quantified, and results were validated with conventional histology.

Main Results:

• Significant differences in FA were observed in the cortex between wild-type and 5xFAD mice at 4 months (p=0.028).
• FA values showed a gradual decrease with age in the cortex and fornix of 5xFAD mice.
• FA and MD demonstrated significant age-dependent differences in the corpus callosum (p=0.029 and p=0.037, respectively); FA was more sensitive than MD in capturing microstructural alterations.

Conclusions:

• Fractional anisotropy (FA) is highly sensitive for monitoring amyloid deposition in 5xFAD mice.
• DTI shows promise as a sensitive biomarker for tracking beta-amyloid progression in preclinical Alzheimer's disease studies.
• High-resolution DTI can effectively characterize age-dependent microstructural changes in mouse models.