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Cited by 51Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAdvanced MRI Techniques and Applications

Imaging the accumulation and suppression of tau pathology using multiparametric MRI

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Holmes, Holly E., Colgan, Niall, Ismail, Ozama, Ma, Da, Powell, Nick M., O'Callaghan, James M., Harrison, Ian F., Johnson, Ross A. +13 more·2016·Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2015.12.001PMC PMC4782737
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Abstract

Mouse models of Alzheimer's disease have served as valuable tools for investigating pathogenic mechanisms relating to neurodegeneration, including tau-mediated and neurofibrillary tangle pathology-a major hallmark of the disease. In this work, we have used multiparametric magnetic resonance imaging (MRI) in a longitudinal study of neurodegeneration in the rTg4510 mouse model of tauopathy, a subset of which were treated with doxycycline at different time points to suppress the tau transgene. Using this paradigm, we investigated the sensitivity of multiparametric MRI to both the accumulation and suppression of pathologic tau. Tau-related atrophy was discernible from 5.5 months within the cortex and hippocampus. We observed markedly less atrophy in the treated rTg4510 mice, which was enhanced after doxycycline intervention from 3.5 months. We also observed differences in amide proton transfer, cerebral blood flow, and diffusion tensor imaging parameters in the rTg4510 mice, which were significantly less altered after doxycycline treatment. We propose that these non-invasive MRI techniques offer insight into pathologic mechanisms underpinning Alzheimer's disease that may be important when evaluating emerging therapeutics targeting one of more of these processes.

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  • Behavioural analysis revealed cognitive deficits in learning and motor tasks.

    “Behavioural analysis revealed cognitive deficits in learning and motor tasks [30,31].”

    From Diffusion tensor imaging reveals whole-brain microstructural changes in the P301L mouse model of tauopathy. (2020) · cites this paper as [30]

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Authors
Holmes, H. E., Colgan, N., Ismail, O., Ma, D., Powell, N. M., O'Callaghan, J. M., Harrison, I. F., Johnson, R. A., Murray, T. K., Ahmed, Z., Heggenes, M., Fisher, A., Cardoso, M. J., Modat, M., Walker-Samuel, S., Fisher, E. M. C., Ourselin, S., O'Neill, M. J., Wells, J. A., Collins, E. C., & Lythgoe, M. F.
Affiliations
  • University College London (GB)
  • Eli Lilly (United States) (US)
  • Eli Lilly (United Kingdom) (GB)
  • UCL Queen Square Institute of Neurology (GB)
Corresponding author
Holmes, Holly E.
ORCID
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2016-03
Volume
39
Pages
184-194
ISSN
0197-4580 (ISSN-L)
DOI
10.1016/j.neurobiolaging.2015.12.001
PMC
PMC4782737
OpenAlex
W2206932523
Cited by
51
References
9
Citations by year
2026: 1 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 5 · 2018: 5 · 2017: 8 · 2016: 1
FWCI
3.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurobiology of Aging (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, cc-by)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • NC3Rs (NC/K500276/1)
  • UK Medical Research Council (MR/G0900207-3/1, MR/J500422/1)
  • EPSRC (EP/H046410/1, EP/J020990/1, EP/K005278)
  • Leonard Wolfson Experimental Neurology Centre (PR/ylr/18575)
  • Wellcome Trust (WT100247MA)
  • MRC (MR/J01107X/1, MR/J013110/1)
  • Medical Research Council (MR/J013110/1)
  • King’s College London
  • Eli Lilly and Company
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Keywords
tau pathology, Alzheimer's disease, doxycycline, neurodegeneration, brain atrophy, amide proton transfer, cerebral blood flow, diffusion tensor imaging, multiparametric MRI, neurofibrillary tangles, hippocampus, cortex
MeSH terms
Alzheimer Disease, Animals, Atrophy, Cerebral Cortex, Disease Models, Animal, Doxycycline, Female, Hippocampus, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mice, Transgenic, Neurofibrillary Tangles, tau Proteins, Transgenes, Tauopathies

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