Voxel-based diffusion tensor imaging of an APP/PS1 mouse model of Alzheimer’s disease.
Abstract
Increasing evidence has demonstrated that white matter (WM) disruptions, due to the injury of the axon and myelin, play an important role in the pathogenesis of Alzheimer's disease (AD). Diffusion tensor imaging (DTI) is a sensitive modality to evaluate the WM integrity in both AD patients and animal models. In this study, an advanced DTI modality, employing a 7.0-T magnetic resonance imaging system, was used to analyze WM changes across the whole brain of an amyloid precursor protein/presenilin 1 (APP/PS1) mouse model. A voxel-based analysis was used to compare the quantitative DTI parameters automatically in both APP/PS1 mice (n = 9) and wild-type (WT) controls (n = 9). After DTI examination, the ultrastructure analysis was compared with DTI findings. Compared with WT controls, gray matter (GM) areas in APP/PS1 mice such as the cingulate cortex and the striatum showed significant fractional anisotropy (FA) and axial diffusivity (DA) increase, while the thalamus only showed a significant FA increase (p < 0.01). Similarly, a significant mean diffusivity, DA, and radial diffusivity increase was observed in the bilateral neocortex (p < 0.01). The left hippocampus only showed significant FA increase in APP/PS1 mice (p < 0.01). The changes in WM regions were detected in the forceps minor of the corpus callosum, the anterior part of the anterior commissure, and the internal capsule, with a significant FA or DA increase (p < 0.01). Abnormalities derived from diffusion measurements were in-line with the ultrastructure findings, including extensive pathological damage of the neurons, neutrophils, and vessels. In conclusion, voxel-based diffusion tensor imaging can detect diffusion alterations not only in GM but also in WM areas in AD models, reflecting the extensive pathological changes of AD.
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Only FA showed a significant increase in the hippocampus of APP/PS1 mice, compared to other DTI metrics.
“It has been reported that only FA showed a significant increase in the hippocampus of APP/PS1 mice, compared to other DTI metrics (Shu et al., 2013).”
From Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging (2022) · cites this paper as Shu et al., 2013
AxD is thought to represent diffusion along the lengths of fibers, and its reduction could be caused by cytoskeletal breakdown or focal 'beading' along axons.
“AxD is thought to represent the diffusion along the lengths of fibers, whose reduction could be caused by cytoskeletal breakdown or focal ‘beading’ along axons 55.”
From Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model (2019) · cites this paper as [55]
The authors' dMRI results are generally consistent with those reported using other mouse models of AD.
“Our dMRI results are generally consistent with those reported using other mouse models of AD [31–35].”
From Brain microstructure abnormalities in the 3xTg-AD mouse – A diffusion MRI and morphology correlation study (2022) · cites this paper as [35]
In the APP/PS1 mouse model of AD, significant FA and AD λ// increase was found in the cingulate cortex and striatum; FA increases in the thalamus, MD and RD λ⊥ increases in the bilateral neocortex, and FA increases in the left hippocampus.
“As an example, in the APP/PS1 mouse model of AD a significant FA and AD λ// increase was found in the cingulate cortex and striatum; in addition to FA increases in the thalamus, MD and RD λ⊥ increases in the bilateral neocortex, and FA increases in the left hippocampus (Shu et al., 2013).”
From Early stage alterations in white matter and decreased functional interhemispheric hippocampal connectivity in the 3xTg mouse model of Alzheimer’s disease. (2019) · cites this paper as Shu et al., 2013
Diffusion tensor imaging in the APP/PS1 model revealed a fractional anisotropy difference map overlapping with our results, including increased FA in the minor forceps.
“Diffusion tensor imaging in the APP/PS1 model revealed a FA difference map overlapping with our results, including increased FA in the minor forceps (Shu et al., 2013).”
From Early Alterations in Functional Connectivity and White Matter Structure in a Transgenic Mouse Model of Cerebral Amyloidosis (2014) · cites this paper as Shu et al., 2013
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- Authors
- Shu, X., Qin, Y.-Y., Zhang, S., Jiang, J.-J., Zhang, Y., Zhao, L.-Y., Shan, D., & Zhu, W.-Z.
- Affiliations
- Wuhan Union Hospital (CN)
- Tongji Hospital (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Shan, Dai
- Venue
- Molecular Neurobiology
- Published
- 2013-03-06
- Volume
- 48
- Issue
- 1
- Pages
- 78-83
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2084136386
- Cited by
- 41
- References
- 31
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 3
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, APP/PS1 mice, white matter integrity, fractional anisotropy, axial diffusivity, mean diffusivity, radial diffusivity, amyloid precursor protein, presenilin 1, corpus callosum, anterior commissure, internal capsule, hippocampus, cingulate cortex, striatum, thalamus, neocortex
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Hippocampus, Mice, Transgenic, Amyloid beta-Protein Precursor, Anisotropy, Neocortex, Mice, Presenilin-1, Diffusion Tensor Imaging
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