Journal
NEUROBIOLOGY OF AGING
Volume 39, Issue -, Pages 184-194Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.12.001
Keywords
Alzheimer's disease; MRI; Biomarker; Longitudinal; Tauopathy; In vivo
Categories
Funding
- NC3Rs studentship [NC/K500276/1]
- UK Medical Research Council Doctoral Training Grant Studentship [MR/G0900207-3/1, MR/J500422/1]
- EPSRC [EP/H046410/1, EP/J020990/1, EP/K005278]
- UCL Leonard Wolfson Experimental Neurology Centre [PR/ylr/18575]
- Wellcome Trust fellowship [WT100247MA]
- MRC [MR/J01107X/1, MR/J013110/1]
- EU-FP7 project VPH-DARE@IT [FP7-ICT-2011-9-601055]
- National Institute for Health Research (NIHR) Biomedical Research Unit (Dementia) at UCL
- National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High-Impact Initiative) [BW.mn.BRC10269]
- Wellcome Trust Joint Senior Investigator Award [098327]
- Medical Research Council [MR/J013110/1]
- UK Regenerative Medicine Platform Safety Hub [MRC: MR/K026739/1, IRIS 104393]
- King's College London
- UCL Comprehensive Cancer Imaging Centre CR-UK EPSRC [000012287]
- MRC (England)
- DoH (England)
- Eli Lilly and Company
- EPSRC [EP/J020990/1, EP/H046410/1] Funding Source: UKRI
- MRC [MR/J01107X/1, MR/K026739/1, MR/J013110/1] Funding Source: UKRI
- Cancer Research UK [16463] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/H046410/1, EP/J020990/1] Funding Source: researchfish
- Medical Research Council [MR/J01107X/1, MR/K026739/1, MR/J013110/1] Funding Source: researchfish
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/K500276/1] Funding Source: researchfish
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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. (C) 2016 The Authors. Published by Elsevier Inc.
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