Assessment of complementary white matter microstructural changes and grey matter atrophy in a preclinical model of Alzheimer's disease

Document Type

Article

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.

Keywords

3xTg-AD mouse, Alzheimer's disease, Free-water diffusion MRI, Voxel-based morphometry

Medical Subject Headings

Mice; Animals; Alzheimer Disease (pathology); Gray Matter (pathology); Diffusion Tensor Imaging (methods); White Matter (pathology); Brain (pathology); Atrophy (pathology)

Publication Date

9-1-2023

Publication Title

Magnetic resonance imaging

E-ISSN

1873-5894

Volume

101

First Page

57

Last Page

66

PubMed ID

37028608

Digital Object Identifier (DOI)

10.1016/j.mri.2023.03.024

Link to Full Text

Share

COinS