Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer's disease
Open accessAbstract
Increased hyperphosphorylated tau and the formation of intracellular neurofibrillary tangles are associated with the loss of neurons and cognitive decline in Alzheimer's disease, and related neurodegenerative conditions. We applied two diffusion models, diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to in vivo diffusion magnetic resonance images (dMRI) of a mouse model of human tauopathy (rTg4510) at 8.5months of age. In grey matter regions with the highest degree of tau burden, microstructural indices provided by both NODDI and DTI discriminated the rTg4510 (TG) animals from wild type (WT) controls; however only the neurite density index (NDI) (the volume fraction that comprises axons or dendrites) from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein. Reductions in diffusion directionality were observed when implementing both models in the white matter region of the corpus callosum, with lower fractional anisotropy (DTI) and higher orientation dispersion (NODDI) observed in the TG animals. In comparison to DTI, histological measures of tau pathology were more closely correlated with NODDI parameters in this region. This in vivo dMRI study demonstrates that NODDI identifies potential tissue sources contributing to DTI indices and NODDI may provide greater specificity to pathology in Alzheimer's disease.
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In a mouse model of tau pathology, NDI in WM and hippocampus was reduced, and NDI in GM was positively correlated with the level of hyperphosphorylated tau protein.
“In a mouse model of tau pathology, NDI in WM and hippocampus was reduced, and NDI in GM was positively correlated with the level of hyperphosphorylated tau protein (Colgan et al., 2016).”
From NODDI in clinical research (2020) · cites this paper as Colgan et al., 2016
The Results (Hippocampus and Corpus callosum; page unavailable) report lower NDI in the tau-model mice, supporting the reduction in hippocampus and white matter. The Results (Cortex and Hippocampus; page unavailable) report correlations between NDI and tau burden in grey matter, but do not establish the claimed positive direction; they report higher cortical NDI but lower hippocampal NDI in the model mice. (LLM, conf=0.86)
Experimental — accuracy not yet measuredNODDI may provide greater specificity to pathology in Alzheimer's disease.
“Colgan et al. demonstrated that only NDI from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein and NODDI may provide greater specificity to pathology in Alzheimer’s disease (Colgan et al. 2016).”
From Neurite orientation dispersion and density imaging of mouse brain microstructure (2019) · cites this paper as Colgan et al. 2016
Only NDI from the NODDI model correlated with histological measurements of hyperphosphorylated tau protein levels.
“Colgan et al. demonstrated that only NDI from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein and NODDI may provide greater specificity to pathology in Alzheimer’s disease (Colgan et al. 2016).”
From Neurite orientation dispersion and density imaging of mouse brain microstructure (2019) · cites this paper as Colgan et al. 2016
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Cites
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“correlated with the level of hyperphosphorylated tau protein (Colgan et al., 2016).”
BackgroundThe use of neuroimaging techniques in the early and differential diagnosis of dementia
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“In dementia, NODDI has been studied in young onset AD [92, 93] showing it is affected in regions associated with early atrophy in AD while NODDI measures in animals correlate with tau burden [94].”
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“…as diffusion kurtosis imaging (DKI; Jensen et al., 2005; Chen et al., 2017; Cheng et al., 2018; Wang et al., 2018), and multi-compartment models such as neurite orientation dispersion and density imaging (NODDI; Zhang et al., 2012; Colgan et al., 2016; Slattery et al., 2017; Parker et al., 2018).”
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“…such as neurite orientation dispersion and density imaging (NODDI), have been used to profile neurite density indexes (NDI) and orientation dispersion indexes (ODI) (Wang et al., 2019) in the mouse models of Aβ amyloidosis (Colon-Perez et al., 2019) and tau pathology (Colgan et al., 2016).”
MethodWang, W., Wen, X., Zhang, Y., Wang, H., Hu, L., Tan, C., & Liu, Z. (2026) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2026.1924031
- Authors
- Colgan, N., Siow, B., O'Callaghan, J. M., Harrison, I. F., Wells, J. A., Holmes, H. E., Ismail, O., Richardson, S., Alexander, D. C., Collins, E. C., Fisher, E. M., Johnson, R., Schwarz, A. J., Ahmed, Z., O'Neill, M. J., Murray, T. K., Zhang, H., & Lythgoe, M. F.
- Affiliations
- University Hospital Galway (IE)
- University College London (GB)
- Eli Lilly (United States) (US)
- National Hospital for Neurology and Neurosurgery (GB)
- Eli Lilly (United Kingdom) (GB)
- Corresponding author
- Colgan, N.
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 125
- Pages
- 739-744
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC4692518
- OpenAlex
- W2206024306
- Cited by
- 218
- References
- 7
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 23 · 2023: 20 · 2022: 24 · 2021: 35 · 2020: 24 · 2019: 26 · 2018: 17 · 2017: 16 · 2016: 4 · 2014: 1
- FWCI
- 10.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- NeuroImage (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (acceptedVersion, cc-by-nc-nd)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion)
- ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (submittedVersion, cc-by-nc-nd)
- UCL Discovery (University College London) (submittedVersion)
- ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (submittedVersion, cc-by-nc)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Research Repository UCD (University College Dublin) (cc-by-nc)
- Funders
- Medical Research Council (MR/J013110/1)
- King's College London and UCL Comprehensive Cancer Imaging Centre CR-UK & EPSRC (000012287)
- MRC (MR/K026739/1, MR/J013110/1)
- Eli Lily and Company (IRIS 104393)
- UK Regenerative Medicine Platform Safety Hub
- NC3Rs studentship (NC/K500276/1)
- UK Medical Research Council Doctoral Training Grant Studentship (MR/J500422/1, MR/G0900207-3/1)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- NODDI, diffusion tensor imaging, Alzheimer's disease, tau pathology, hyperphosphorylated tau, neurite density index, corpus callosum, fractional anisotropy, orientation dispersion, grey matter, white matter, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Brain, Brain Mapping, Disease Models, Animal, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Mice, Transgenic, Neurites, Neurofibrillary Tangles, tau Proteins, Anisotropy, Mice, Diffusion Tensor Imaging
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