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Cited by 22Advanced Neuroimaging Techniques and ApplicationsAdvanced MRI Techniques and ApplicationsDementia and Cognitive Impairment Research

Diffusion MRI detects longitudinal white matter changes in the 3xTg-AD mouse model of Alzheimer's disease

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Nie, Xingju, Falangola, Maria Fatima, Ward, Ralph, McKinnon, Emilie T., Helpern, Joseph A., Nietert, Paul J., Jensen, Jens H.·2019·Magnetic Resonance Imaging
DOI 10.1016/j.mri.2018.12.003PMC PMC6331227
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Abstract

The sensitivity of multiple diffusion MRI (dMRI) parameters to longitudinal changes in white matter microstructure was investigated for the 3xTg-AD transgenic mouse model of Alzheimer's disease, which manifests both amyloid beta plaques and neurofibrillary tangles. By employing a specific dMRI method known as diffusional kurtosis imaging, eight different diffusion parameters were quantified to characterize distinct aspects of water diffusion. Four female 3xTg-AD mice were imaged at five time points, ranging from 4.5 to 18 months of age, and the diffusion parameters were investigated in four white matter regions (fimbria, external capsule, internal capsule and corpus callosum). Significant changes were observed in several diffusion parameters, particularly in the fimbria and in the external capsule, with a statistically significant decrease in diffusivity and a statistically significant increase in kurtosis. Our preliminary results demonstrate that dMRI can detect microstructural changes in white matter for the 3xTg-AD mouse model due to aging and/or progression of pathology, depending strongly on the diffusion parameter and anatomical region.

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  • The authors found that dMRI metrics change longitudinally with aging and AD pathology progression in several brain regions.

    “Moreover, we found that dMRI metrics change longitudinally with aging [16] and AD pathology progression [17] in several brain regions.”

    From Brain microstructure abnormalities in the 3xTg-AD mouse – A diffusion MRI and morphology correlation study (2022) · cites this paper as [17]

    The Results report longitudinal changes in dMRI measures across several white-matter regions of 3xTg-AD mice. The Discussion suggests that some changes accompany AD-like pathology progression, but says the absence of a control group prevents separating pathology-related changes from aging; it does not establish that progression caused the measured changes. Page numbers were not provided. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The inconsistent findings among DTI studies suggest that age-related diffusion metrics changes in the 3×Tg-AD mouse model are complex.

    “The inconsistent findings among these DTI studies suggest that age-related diffusion metrics changes in the 3×Tg-AD mouse model are complex (Nie et al., 2019).”

    From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Nie et al., 2019

    The Discussion describes conflicting diffusion-metric findings across studies and notes that methodological differences make direct comparison difficult. It also says there was only one prior dMRI study of white matter in 3xTg-AD mice, and that study did not report age-related trajectories. Thus, the paper supports complexity in interpreting the changes, but not inconsistent age-related findings among multiple DTI studies of this specific model. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Other studies conducted on the same model in mice at ages 2, 12, and 14 months identified significant WM alterations.

    “Conversely, other studies conducted on the same model in mice at ages 2, 12, and 14 months identified significant WM alterations (Manno et al., 2019; Nie et al., 2019; Falangola et al., 2021).”

    From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Nie et al., 2019

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Cited by

Sorted by citations

Authors
Nie, X., Falangola, M. F., Ward, R., McKinnon, E. T., Helpern, J. A., Nietert, P. J., & Jensen, J. H.
Affiliations
Medical University of South Carolina (US)
Corresponding author
Nie, Xingju
ORCID
Venue
Magnetic Resonance Imaging
Publisher
Elsevier BV
Published
2019-04
Volume
57
Pages
235-242
ISSN
0730-725X (ISSN-L)
DOI
10.1016/j.mri.2018.12.003
PMC
PMC6331227
OpenAlex
W2904488874
Cited by
22
References
7
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 1
FWCI
1.38
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Magnetic Resonance Imaging (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (1RF1AG057602-01, T32DC014435)
  • The Litwin Foundation
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
diffusion MRI, white matter microstructure, Alzheimer's disease, 3xTg-AD mice, diffusion kurtosis imaging, longitudinal change, fimbria, external capsule, internal capsule, corpus callosum, amyloid plaques, neurofibrillary tangles, aging, water diffusion
MeSH terms
Alzheimer Disease, Animals, Disease Models, Animal, Female, Humans, Mice, Transgenic, Neurofibrillary Tangles, Disease Progression, Diffusion Magnetic Resonance Imaging, Mice, Plaque, Amyloid, White Matter

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