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Published on: April 19, 2021
Assessment of complementary white matter microstructural changes and grey matter atrophy in a preclinical model of
Maurizio Bergamino1, Megan R Nelson1, Asfia Numani1
1Division of Neuroimaging Research, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
Abstract:
Alzheimer's disease (AD) has been associated with amyloid and tau pathology, as well as neurodegeneration. Beyond these hallmark features, white matter microstructural abnormalities have been observed using MRI. The objective of this study was to assess grey matter atrophy and white matter microstructural changes in a preclinical mouse model of AD (3xTg-AD) using voxel-based morphometry (VBM) and free-water (FW) diffusion tensor imaging (FW-DTI). Compared to controls, lower grey matter density was observed in the 3xTg-AD model, corresponding to the small clusters in the caudate-putamen, hypothalamus, and cortex. DTI-based fractional anisotropy (FA) was decreased in the 3xTg model, while the FW index was increased. Notably, the largest clusters for both FW-FA and FW index were in the fimbria, with other regions including the anterior commissure, corpus callosum, forebrain septum, and internal capsule. Additionally, the presence of amyloid and tau in the 3xTg model was confirmed with histopathology, with significantly higher levels observed across many regions of the brain. Taken together, these results are consistent with subtle neurodegenerative and white matter microstructural changes in the 3xTg-AD model that manifest as increased FW, decreased FW-FA, and decreased grey matter density.
Insights
This study reveals early white matter changes in a preclinical Alzheimer
Area of Science:
- Neuroscience
- Biomedical Imaging
- Neuropathology
Background:
- Alzheimer's disease (AD) is characterized by amyloid and tau pathology and neurodegeneration.
- White matter microstructural abnormalities are increasingly recognized in AD.
- Preclinical models are crucial for understanding early AD pathogenesis.
Purpose of the Study:
- To investigate grey matter atrophy and white matter changes in the 3xTg-AD mouse model.
- To utilize voxel-based morphometry (VBM) and free-water diffusion tensor imaging (FW-DTI).
- To correlate imaging findings with amyloid and tau pathology.
Main Methods:
- Voxel-based morphometry (VBM) for grey matter density analysis.
- Free-water diffusion tensor imaging (FW-DTI) to assess white matter microstructure.
- Histopathology to confirm amyloid and tau burden.
Main Results:
- Reduced grey matter density in the caudate-putamen, hypothalamus, and cortex of 3xTg-AD mice.
- Decreased fractional anisotropy (FA) and increased free-water (FW) index in white matter tracts.
- Significant increases in amyloid and tau levels confirmed via histopathology.
Conclusions:
- The 3xTg-AD mouse model exhibits early grey matter atrophy and white matter microstructural alterations.
- Increased FW and decreased FW-FA indicate subtle white matter changes preceding overt neurodegeneration.
- These findings highlight the utility of FW-DTI in detecting early AD-related white matter pathology.
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