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In Vivo Positron Emission Tomographic Imaging of Glial Responses to Amyloid-β and Tau Pathologies in Mouse Models of Alzheimer's Disease and Related Disorders
Open accessAbstract
Core pathologies of Alzheimer's disease (AD) are aggregated amyloid-β peptides (Aβ) and tau, and the latter is also characteristic of diverse neurodegenerative tauopathies. These amyloid lesions provoke microglial activation, and recent neuroimaging technologies have enabled visualization of this response in living brains using radioligands for the peripheral benzodiazepine receptor also known as the 18 kDa translocator protein (TSPO). Here, we elucidated contributions of Aβ and tau deposits to in vivo TSPO signals in pursuit of mechanistic and diagnostic significance of TSPO imaging in AD and other tauopathies. A new antibody to human TSPO revealed induction of TSPO-positive microgliosis by tau fibrils in tauopathy brains. Emergence of TSPO signals before occurrence of brain atrophy and thioflavin-S-positive tau amyloidosis was also demonstrated in living mice transgenic for mutant tau by positron emission tomography (PET) with two classes of TSPO radioligands, [11 C]AC-5216 and [18 F]fluoroethoxy-DAA1106. Meanwhile, only modest TSPO elevation was observed in aged mice modeling Aβ plaque deposition, despite the notably enhanced in vivo binding of amyloid radiotracer, [11 C]Pittsburgh Compound-B, to plaques. In these animals, [11 C]AC-5216 yielded better TSPO contrasts than [18 F]fluoroethoxy-DAA1106, supporting the possibility of capturing early neurotoxicity with high-performance TSPO probes. Furthermore, an additional line of mice modeling intraneuronal Aβ accumulation displayed elevated TSPO signals following noticeable neuronal loss, unlike TSPO upregulation heralding massive neuronal death in tauopathy model mice. Our data corroborate the utility of TSPO-PET imaging as a biomarker for tau-triggered toxicity, and as a complement to amyloid scans for diagnostic assessment of tauopathies with and without Aβ pathologies.
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“TPSO signal has been shown to increase with microglia activation in tauopathies including AD, PSP, PiD, and FTDP-17 [111–113] as well as several other neurodegenerative diseases and injury models such as other frontotemporal dementias (FTDs), Parkinson’s disease, stroke and TBI [114].”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [111]
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“Importantly, TPSO signaling preceded thioflavin-S-positive tangles and MRI-measureable regional atrophy in the mice implying TPSO PET may be more adept at detecting neuroinflammation induced by tau aggregation [111].”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [111]
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Cites
Spillantini, M. G., Schmidt, M. L., Lee, V. M.-Y., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997) · Nature · doi:10.1038/42166 · Cited by 8,382
Self-citationUbiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576
Self-citationImaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208
Self-citationTau Suppression in a Neurodegenerative Mouse Model Improves Memory Function
SantaCruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., et al. (2005) · Science · doi:10.1126/science.1113694 · Cited by 2,014
Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data
Logan, J., Fowler, J. S., Volkow, N. D., Wang, G., Ding, Y., & Alexoff, D. L. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199609000-00008 · Cited by 1,515
Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology
Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K.-H., Mistl, C., Rothacher, S., Ledermann, B., Bürki, K., Frey, P., Paganetti, P. A., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.13287 · Cited by 1,507
Self-citationMCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287 · cited 1×
“It is well known that amyloid deposition triggers microglial and astroglial activation in AD brains (McGeer and McGeer, 1995).”
BackgroundJack, C. R., Lowe, V. J., Weigand, S. D., Wiste, H. J., Senjem, M. L., Knopman, D. S., Shiung, M. M., Gunter, J. L., Boeve, B. F., Kemp, B. J., et al. (2009) · Brain · doi:10.1093/brain/awp062 · Cited by 1,099
Flagged first, then by citations
Research works printed but not linked: 1
- Takeuchi, 2009, Development of therapies and monitoring for tauopathies with dementia, Soc Neurosci Abstr, 35, 236
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Sorted by citations
Items 101–137 of 137
Cao, Q. C., Meng, T., Man, J., Peng, D., Chen, H., Xiang, Q., Su, Z., Zhang, Q., & Huang, Y. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190458 · Cited by 13
18F-PBR06 PET/CT imaging for evaluating atherosclerotic plaques linked to macrophage infiltration
Zhang, H., Xiao, J., Zhou, J., Tan, H., Hu, Y., Mao, W., Fu, Z., Lin, Q., Shi, H., & Cheng, D. (2019) · Nuclear Medicine Communications · doi:10.1097/mnm.0000000000000978 · Cited by 11
Basic Science of PET Imaging for Inflammatory Diseases
Kubota, K., Ogawa, M., Ji, B., Watabe, T., Zhang, M., Suzuki, H., Sawada, M., Nishi, K., & Kudo, T. (2019) · Springer eBooks · doi:10.1007/978-981-15-0810-3_1 · Cited by 12
Self-citationKumata, K., Yui, J., Hatori, A., Fujinaga, M., Yanamoto, K., Yamasaki, T., Kawamura, K., Wakizaka, H., Nengaki, N., Yoshida, Y., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200516a · Cited by 11
Self-citationA lzheimer's Disease Biomarkers: More Than Molecular Diagnostics
Anderson, D. C. (2013) · Drug Development Research · doi:10.1002/ddr.21073 · Cited by 9
Diagnostic and therapeutic targeting of pathological tau proteins in neurodegenerative disorders
Sahara, N., & Higuchi, M. (2023) · FEBS Open Bio · doi:10.1002/2211-5463.13711 · Cited by 9
Self-citationIn vivo imaging of neuroinflammation in Alzheimer's disease
Higuchi, M., Ji, B., Maeda, J., Sahara, N., & Suhara, T. (2016) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12308 · Cited by 8
Self-citationYang, Z., Banks, S. J., Ritter, A. R., Cummings, J. L., Sreenivasan, K. R., Kinney, J. W., Caldwell, J. K., Wong, C. G., Miller, J. B., & Cordes, D. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230631 · Cited by 9
Joshi, J., Yao, M., Kakazu, A., Ouyang, Y., Duan, W., & Aggarwal, M. (2025) · Imaging Neuroscience · doi:10.1162/imag_a_00467 · Cited by 7
Bay, S., Digwal, C. S., Martín, A. M. R., Sharma, S., Stanisavljevic, A., Rodina, A., Attaran, A., Roychowdhury, T., Parikh, K., Toth, E., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12061252 · Cited by 6
Genetic and degenerative disorders primarily causing dementia
Masdeu, J. C., & Pascual, B. (2016) · Handbook of clinical neurology · doi:10.1016/b978-0-444-53485-9.00026-x · Cited by 6
Takuwa, H., Orihara, A., Takado, Y., Urushihata, T., Shimojo, M., Ishikawa, A., Takahashi, M., Barron, A. M., Ono, M., Maeda, J., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.04.368977 · Cited by 6
Self-citationPET Applications in Animal Models of Neurodegenerative and Neuroinflammatory Disorders
Higuchi, M., Maeda, J., Ji, B., Tokunaga, M., Zhang, M., Maruyama, M., Ono, M., Fukumura, T., & Suhara, T. (2011) · Current topics in behavioral neurosciences · doi:10.1007/7854_2011_167 · Cited by 5
Self-citationIs the Voltage-Dependent Anion Channel a Major Player in Neurodegenerative Diseases?
Neumann, S., & Heumann, R. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136138 · Cited by 5
Lacivita, E., Stama, M. L., Maeda, J., Fujinaga, M., Hatori, A., Zhang, M., Colabufo, N. A., Perrone, R., Higuchi, M., Suhara, T., et al. (2016) · Chemistry & Biodiversity · doi:10.1002/cbdv.201500281 · Cited by 4
Self-citationGenetically targeted reporter imaging of deep neuronal network in the mammalian brainPreprint
Shimojo, M., Ono, M., Takuwa, H., Mimura, K., Nagai, Y., Fujinaga, M., Kikuchi, T., Okada, M., Seki, C., Tokunaga, M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.08.032870 · Cited by 4
Self-citationNonamyloid Pet Biomarkers and Alzheimer'S Disease: Current and Future Perspectives
Schilling, L. P., Leuzy, A., Zimmer, E. R., Gauthier, S. G., & Rosa‐Neto, P. (2014) · Future Neurology · doi:10.2217/fnl.14.40 · Cited by 4
Epichaperome-targeted myocardial imaging by 124I-PU-H71 PET
Mahajan, S., Grkovski, M., Staton, K. D., Ravassa, S., Domfe, K., Strausś, H. W., Humm, J. L., ZANZONICO, P. B., Beattie, B. J., Cho, I., et al. (2024) · Clinical and Translational Imaging · doi:10.1007/s40336-024-00658-9 · Cited by 2
Ni, R. (2015) · Figshare · Cited by 2
A practical process for the synthesis of translocator protein 18kDa imidazopyridine ligand
Wen, M., Qu, C., Su, X., Ding, M., Deng, Z., & Hong, X. (2014) · Wuhan University Journal of Natural Sciences · doi:10.1007/s11859-014-0973-9 · Cited by 1
Chronic Neuroinflammation Underlying Pathogenesis of Alzheimer’s Disease
Saito, T. (2016) · Springer eBooks · doi:10.1007/978-4-431-56068-5_50 · Cited by 1
Neuroimaging Biomarkers in Alzheimer’s Disease and Related Disorders
Masdeu, J. C., & Pascual, B. (2023) · Springer eBooks · doi:10.1007/978-3-031-43356-6_11 · Cited by 1
Review Article Alzheimer's disease biomarkers in animal models: closing the translational gap
Sabbagh, J. J., Kinney, J. W., Cummings, J. L., & Ruvo, L. (2013)
The translocator protein as a drug target in Alzheimer's
Chua, S. W., Kassiou, M., & Ittner, L. M. (2014)
Wu, C., Yue, X., Lang, L., Kiesewetter, D. O., Li, F., Zhu, Z., Niu, G., & Chen, X. (2014)
Linking Molecular Neurobiology to Therapeutic Approaches for Alzheimer’s Disease with PET
Luiten, P. G. M., Masman, M. F., Dobos, N., Nyakas, C. J., de Vries, E. F. J., Dierckx, R., & Eisel, U. L. M. (2014) · Springer eBooks · doi:10.1007/978-3-642-54307-4_20
Molecular Imaging in Alzheimer Clinical Trials
Schmidt, M. E., Matthews, D. C., & Staelens, S. G. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802173-6.00020-4
Jadhav, V. (2021) · IUScholarWorks (Indiana University) · doi:10.7912/c2/2086
Preclinical Longitudinal In Vivo Biomarker Platform for Alzheimer’s Disease Drug Discovery
Kang, M. S., Zimmer, E. R., Ottoy, J., Shin, M., Woo, M. S., Aliaga, A., Massarweh, G., Cuello, A. C., Gauthier, S. G., & Rosa‐Neto, P. (2022) · Cambridge University Press eBooks · doi:10.1017/9781108975759.010
Therapeutic and immunomodulatory functions of the translocator protein in Alzheimer's disease
Fairley, L. H. (2022) · DR-NTU (Nanyang Technological University) · doi:10.32657/10356/160865
Positron emission tomography imaging of neuroinflammation
(2023) · Advances in magnetic resonance technology and applications · doi:10.1016/b978-0-323-91771-1.00007-1
Fujinaga, M., Ohkubo, T., Shimojo, M., Nagai, Y., Ono, M., Matsushita, Y., Mimura, K., Mori, W., Zhang, Y., Kurihara, Y., et al. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c00613 · Cited by 1
Self-citationFairley, L. H., Sahara, N., Aoki, I., Ji, B., Suhara, T., Higuchi, M., & Barron, A. M. (2021) · Figshare · doi:10.6084/m9.figshare.14252304
Self-citationEckenweber, F., Medina-Luque, J., Blume, T., Sacher, C., Biechele, G., Wind, K., Deussing, M., Briel, N., Lindner, S., Boening, G., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12650326
Gallagher, R. L., Koscik, R. L., Moody, J. F., Vogt, N. M., Adluru, N., Kecskemeti, S., Van Hulle, C. A., Chin, N. A., Asthana, S., Kollmorgen, G., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26628052
Role of T-cell immunity in the pathophysiology of Alzheimer’s disease and other Tauopathies
Matta, K. (2024) · theses.fr (ABES) · doi:10.70675/cea4fe5ez67c3z4445z92f7z39af62ba059b
Metadata
- Authors
- Maeda, J., Zhang, M.-R., Okauchi, T., Ji, B., Ono, M., Hattori, S., Kumata, K., Iwata, N., Saido, T. C., Trojanowski, J. Q., Lee, V. M.-Y., Staufenbiel, M., Tomiyama, T., Mori, H., Fukumura, T., Suhara, T., & Higuchi, M.
- Affiliations
- National Institute of Radiological Sciences (JP)
- RIKEN Center for Brain Science (JP)
- University of Pennsylvania (US)
- Novartis (Switzerland) (CH)
- Osaka City University (JP)
- Corresponding author
- Higuchi, Makoto
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-03-23
- Volume
- 31
- Issue
- 12
- Pages
- 4720-4730
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3251921
- OpenAlex
- W2160881303
- Cited by
- 136
- References
- 53
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 9 · 2022: 4 · 2021: 14 · 2020: 14 · 2019: 9 · 2018: 6 · 2017: 7 · 2016: 10 · 2015: 12 · 2014: 17 · 2013: 14 · 2012: 9
- FWCI
- 9.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- National Institutes of Health (AG 10 124, AG 17586)
- Japan Society for the Promotion of Science (20790047, 23390235, 20023036, 22790835)
- National Institute on Aging (P30AG010124, P01AG017586, AG17586, AG-10124)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, tauopathy, translocator protein (TSPO), microglial activation, amyloid plaques, tau fibrils, TSPO PET imaging, Pittsburgh compound B, intraneuronal amyloid-beta, neurodegeneration biomarkers, neuroinflammation
- MeSH terms
- Acetamides, Alzheimer Disease, Aniline Compounds, Animals, Autoradiography, Brain, Humans, Immunohistochemistry, Isotope Labeling, Magnetic Resonance Imaging, Mice, Inbred C57BL, Neuritis, Neuroglia, Purines, Supranuclear Palsy, Progressive, Thiazoles, Amyloid beta-Protein Precursor, tau Proteins, Receptors, GABA, Radiopharmaceuticals, Pick Disease of the Brain, Positron-Emission Tomography, Mice, Plaque, Amyloid
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