Imaging of Tau Pathology in a Tauopathy Mouse Model and in Alzheimer Patients Compared to Normal Controls
Open accessAbstract
Accumulation of intracellular tau fibrils has been the focus of research on the mechanisms of neurodegeneration in Alzheimer's disease (AD) and related tauopathies. Here, we have developed a class of tau ligands, phenyl/pyridinyl-butadienyl-benzothiazoles/benzothiazoliums (PBBs), for visualizing diverse tau inclusions in brains of living patients with AD or non-AD tauopathies and animal models of these disorders. In vivo optical and positron emission tomographic (PET) imaging of a transgenic mouse model demonstrated sensitive detection of tau inclusions by PBBs. A pyridinated PBB, [(11)C]PBB3, was next applied in a clinical PET study, and its robust signal in the AD hippocampus wherein tau pathology is enriched contrasted strikingly with that of a senile plaque radioligand, [(11)C]Pittsburgh Compound-B ([(11)C]PIB). [(11)C]PBB3-PET data were also consistent with the spreading of tau pathology with AD progression. Furthermore, increased [(11)C]PBB3 signals were found in a corticobasal syndrome patient negative for [(11)C]PIB-PET.
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Both models rely on transgene overexpression and familial mutations and are not well suited for studying causative events that lead to development of pathology in sporadic AD.
“Both models rely on transgene overexpression and familial mutations (such as ADAD mutations in 5xFAD mice and frontotemporal dementia mutations in PS19 mice) and are not well suited for studying the causative events that lead to the development of pathology in sporadic AD [44–47].”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [47]
The Experimental Procedures (Animal models; page unavailable) identify PS19 mice as transgenic mice expressing human tau with the FTDP-17 P301S mutation. The paper does not address 5xFAD mice or say that either model is poorly suited to studying causative events in sporadic AD. (LLM, conf=0.87)
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Gordon, B. A., Blazey, T., & Benzinger, T. L. (2014) · Future Neurology · doi:10.2217/fnl.14.9 · Cited by 11 · see citing works
Strobel, J., Müller, H.-P., Ludolph, A. C., Beer, A. J., Sollmann, N., & Kassubek, J. (2023) · Cells · doi:10.3390/cells12242776 · Cited by 10 · see citing works
Human iPSC Models in Drug Discovery: Opportunities and Challenges
Silva, M. C., Cross, A., Brandon, N. J., & Haggarty, S. J. (2017) · Comprehensive Medicinal Chemistry III · doi:10.1016/b978-0-12-409547-2.12284-x · Cited by 6 · see citing works
- Authors
- Maruyama, M., Shimada, H., Suhara, T., Shinotoh, H., Ji, B., Maeda, J., Zhang, M.-R., Trojanowski, J. Q., Lee, V. M.-Y., Ono, M., Masamoto, K., Takano, H., Sahara, N., Iwata, N., Okamura, N., Furumoto, S., Kudo, Y., Chang, Q., Saido, T. C., Takashima, A., Lewis, J., Jang, M.-K., Aoki, I., Ito, H., & Higuchi, M.
- Affiliations
- National Institute of Radiological Sciences (JP)
- University of Pennsylvania (US)
- RIKEN Center for Brain Science (JP)
- Tohoku University (JP)
- Clinical Research, Innovation and Education Center, Tohoku University Hospital (JP)
- The University of Texas MD Anderson Cancer Center (US)
- University of Florida (US)
- Corresponding author
- Higuchi, Makoto
- ORCID
- Shimada, Hitoshi
- Suhara, Tetsuya
- Shinotoh, Hitoshi
- Ji, Bin
- Maeda, Jun
- Trojanowski, John Q.
- Lee, Virginia M.-Y.
- Ono, Maiko
- Masamoto, Kazuto
- Takano, Harumasa
- Sahara, Naruhiko
- Iwata, Nobuhisa
- Okamura, Nobuyuki
- Furumoto, Shozo
- Chang, Qing
- Saido, Takaomi C.
- Takashima, Akihiko
- Lewis, Jada
- Jang, Ming-Kuei
- Aoki, Ichio
- Ito, Hiroshi
- Higuchi, Makoto
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 79
- Issue
- 6
- Pages
- 1094-1108
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3809845
- OpenAlex
- W2009870816
- Cited by
- 760
- References
- 9
- Citations by year
- 2026: 15 · 2025: 36 · 2024: 28 · 2023: 40 · 2022: 49 · 2021: 62 · 2020: 61 · 2019: 50 · 2018: 68 · 2017: 74 · 2016: 103 · 2015: 80 · 2014: 81 · 2013: 13
- FWCI
- 64.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- 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
- Japan Society for the Promotion of Science (23591735, 23390235, 23390297)
- National Institute on Aging (P30AG010124, P01AG017586, AG17586, AG-10124)
- 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 › Medical Imaging Techniques and Applications
- Keywords
- tau pathology, tauopathy, Alzheimer's disease, positron emission tomography, transgenic mouse model, hippocampus, amyloid plaques, corticobasal syndrome, tau spread, neurodegeneration
- MeSH terms
- Age Factors, Aged, Alzheimer Disease, Aminopyridines, Aniline Compounds, Animals, Autoradiography, Brain, Brain Mapping, Calcium-Binding Proteins, Carbon Isotopes, Disease Models, Animal, DNA-Binding Proteins, Dose-Response Relationship, Drug, Female, Humans, Magnetic Resonance Imaging, Male, Mice, Inbred C57BL, Mice, Transgenic, Microfilament Proteins, Middle Aged, Mutation, Thiazoles, Amyloid beta-Peptides, tau Proteins, Protein Structure, Secondary, Tauopathies, Positron-Emission Tomography, Mice, Benzothiazoles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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