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Imaging the accumulation and suppression of tau pathology using multiparametric MRI
Holly E Holmes1, Niall Colgan1, Ozama Ismail1
1Division of Medicine, Centre for Advanced Biomedical Imaging, University College London, London, UK.
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.
Insights
Multiparametric MRI detects tau-related brain atrophy in Alzheimer's disease models. Doxycycline treatment reduced atrophy and altered MRI signals, showing potential for therapeutic evaluation.
Area of Science:
- Neuroscience
- Biomedical Imaging
- Alzheimer's Disease Research
Background:
- Alzheimer's disease (AD) is characterized by neurodegeneration, particularly tau pathology.
- Mouse models are crucial for studying AD mechanisms like tau-mediated neurodegeneration.
- Multiparametric MRI offers non-invasive insights into brain changes.
Purpose of the Study:
- To assess multiparametric MRI's sensitivity to tau accumulation and suppression in a mouse model.
- To longitudinally track neurodegeneration and the effects of therapeutic intervention.
- To evaluate MRI parameters for monitoring Alzheimer's disease progression and treatment response.
Main Methods:
- Longitudinal multiparametric MRI study in the rTg4510 mouse model of tauopathy.
- Doxycycline treatment administered at different time points to suppress tau transgene expression.
- Analysis of MRI parameters including atrophy, amide proton transfer, cerebral blood flow, and diffusion tensor imaging.
Main Results:
- Tau-related atrophy detected in cortex and hippocampus from 5.5 months in rTg4510 mice.
- Significantly reduced atrophy observed in doxycycline-treated mice, with enhanced effects from early intervention.
- Multiparametric MRI parameters showed alterations in tauopathy mice, which were mitigated by doxycycline treatment.
Conclusions:
- Multiparametric MRI can detect and monitor tau-related neurodegeneration in vivo.
- MRI techniques are sensitive to the effects of therapeutic interventions targeting tau pathology.
- Non-invasive MRI methods show promise for evaluating novel Alzheimer's disease therapeutics.
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