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Cited by 70Advanced Neuroimaging Techniques and ApplicationsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

Age-related decline in white matter integrity in a mouse model of tauopathy: an in vivo diffusion tensor magnetic resonance imaging study

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Sahara, Naruhiko, Perez, Pablo D., Lin, Wen-Lang, Dickson, Dennis W., Ren, Yan, Zeng, Huadong, Lewis, Jada, Febo, Marcelo·2014·Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2013.12.009PMC PMC4729397
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Abstract

Elevated expression of human hyperphosphorylated tau is associated with neuronal loss and white matter (WM) pathology in Alzheimer's disease (AD) and related neurodegenerative disorders. Using in vivo diffusion tensor magnetic resonance imaging (DT-MRI) at 11.1 Tesla we measured age-related alterations in WM diffusion anisotropy indices in a mouse model of human tauopathy (rTg4510) and nontransgenic (nonTg) control mice at the age of 2.5, 4.5, and 8 months. Similar to previous DT-MRI studies in AD subjects, 8-month-old rTg4510 mice showed lower fractional anisotropy (FA) values in WM structures than nonTg. The low WM FA in rTg4510 mice was observed in the genu and splenium of the corpus callosum, anterior commissure, fimbria, and internal capsule and was associated with a higher radial diffusivity than nonTg. Interestingly, rTg4510 mice showed lower estimates for the mode of anisotropy than controls at 2.5 months suggesting that changes in this diffusivity metric are detectable at an early stage preceding severe tauopathy. Immunogold electron microscopy partly supports our diffusion tensor imaging findings. At the age of 4 months, rTg4510 mice show axonal tau inclusions and unmyelinated processes. At later ages (12 months and 14 months) we observed inclusions in myelin sheath, axons, and unmyelinated processes, and a "disorganized" pattern of myelinated fiber arrangement with enlarged inter-axonal spaces in rTg4510 but not in nonTg mice. Our data support a role for the progression of tau pathology in reduced WM integrity measured by DT-MRI. Further in vivo DT-MRI studies in the rTg4510 mouse should help better discern the detailed mechanisms of reduced FA and anisotropy mode, and the specific role of tau during neurodegeneration.

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  • These findings are highly concordant with an earlier longitudinal study that applied DTI methods to investigate the white matter of the rTg4510 model.

    “These findings are highly concordant with an earlier longitudinal study that applied DTI methods to investigate the white matter of the rTg4510 model (Sahara et al., 2014).”

    From In vivo imaging of tau pathology using multi-parametric quantitative MRI (2015) · cites this paper as Sahara et al., 2014

    The Results (section 3.2) report DTI measurements of white matter in rTg4510 mice at different ages. But the Methods (section 2.2) describe 29 mice allocated across three age groups, not repeated scans of the same mice; calling this a longitudinal study is unsupported. The citing authors’ assessment of concordance is their own framing. (LLM, conf=0.88)

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  • Electron microscopy measures demonstrated the presence of tau inclusions in the white matter and subsequent micro-structural disorganisation relative to WT controls at later time points.

    “Electron microscopy measures were performed and demonstrated the presence of tau inclusions in the white matter and subsequent micro-structural disorganisation relative to WT controls at later time points (Sahara et al., 2014).”

    From In vivo imaging of tau pathology using multi-parametric quantitative MRI (2015) · cites this paper as Sahara et al., 2014

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Authors
Sahara, N., Perez, P. D., Lin, W.-L., Dickson, D. W., Ren, Y., Zeng, H., Lewis, J., & Febo, M.
Affiliations
  • University of Florida (US)
  • Mayo Clinic in Florida (US)
ORCID
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2014-06
Volume
35
Issue
6
Pages
1364-1374
ISSN
0197-4580 (ISSN-L)
DOI
10.1016/j.neurobiolaging.2013.12.009
PMC
PMC4729397
OpenAlex
W2062131497
Cited by
70
References
7
Citations by year
2026: 6 · 2025: 2 · 2024: 9 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 11 · 2019: 10 · 2018: 5 · 2017: 6 · 2016: 1 · 2015: 6 · 2014: 1
FWCI
1.90
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
  • QST-Repository (National Institutes for Quantum and Radiological Science and Technology) (submittedVersion)
Funders
  • National Institutes of Health (DA019946, NS067127)
  • McKnight Brain Institute
  • University of Florida College of Medicine
  • University of Florida
  • Center for Translational Research in Neurodegenerative Disease and the Department of Neuroscience
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
tauopathy, white matter integrity, rTg4510 mice, hyperphosphorylated tau, Alzheimer's disease, fractional anisotropy, radial diffusivity, corpus callosum, anterior commissure, myelin sheath, neurodegeneration, age-related decline
MeSH terms
Aging, Alzheimer Disease, Animals, Corpus Callosum, Disease Models, Animal, Mice, Transgenic, tau Proteins, Anisotropy, Neurodegenerative Diseases, Tauopathies, Mice, Diffusion Tensor Imaging

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