In vivo imaging of microglial activation by positron emission tomography with [11C]PBR28 in the 5XFAD model of A lzheimer's disease
Open accessAbstract
Microglial activation has been linked with deficits in neuronal function and synaptic plasticity in Alzheimer's disease (AD). The mitochondrial translocator protein (TSPO) is known to be upregulated in reactive microglia. Accurate visualization and quantification of microglial density by PET imaging using the TSPO tracer [11 C]‐R‐PK11195 has been challenging due to the limitations of the ligand. In this study, it was aimed to evaluate the new TSPO tracer [11 C]PBR28 as a marker for microglial activation in the 5XFAD transgenic mouse model of AD. Dynamic PET scans were acquired following intravenous administration of [11 C]PBR28 in 6‐month‐old 5XFAD mice and in wild‐type controls. Autoradiography with [3 H]PBR28 was carried out in the same brains to further confirm the distribution of the radioligand. In addition, immunohistochemistry was performed on adjacent brain sections of the same mice to evaluate the co‐localization of TSPO with microglia. PET imaging revealed that brain uptake of [11 C]PBR28 in 5XFAD mice was increased compared with control mice. Moreover, binding of [3 H]PBR28, measured by autoradiography, was enriched in cortical and hippocampal brain regions, coinciding with the positive staining of the microglial marker Iba‐1 and amyloid deposits in the same areas. Furthermore, double‐staining using antibodies against TSPO demonstrated co‐localization of TSPO with microglia and not with astrocytes in 5XFAD mice and human post‐mortem AD brains. The data provided support of the suitability of [11 C]PBR28 as a tool for in vivo monitoring of microglial activation and assessment of treatment response in future studies using animal models of AD. GLIA 2016;64:993–1006
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Positron emission tomography (PET) is the most widely used in vivo method for detecting microglial activation.
“Positron emission tomography (PET) is the most widely used in vivo method for detecting microglial activation (Owen and Matthews, 2011; Mirzaei et al., 2016).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Mirzaei et al., 2016
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The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma.
Ramirez, A. I., de Hoz, R., Salobrar-Garcia, E., Salazar, J. J., Rojas, B., Ajoy, D., López-Cuenca, I., Rojas, P., Triviño, A., & Ramírez, J. M. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00214 · Cited by 466 · see citing works
Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation
Albrecht, D. S., Forsberg, A., Sandström, A., Bergan, C., Kadetoff, D., Protsenko, E., Lampa, J., Lee, Y. C., Höglund, C. O., Catana, C., et al. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.09.018 · Cited by 310 · see citing works
Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
Condello, C., Yuan, P., & Grutzendler, J. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.10.007 · Cited by 131 · see citing works
Betlazar, C., Harrison-Brown, M., Middleton, R., Banati, R., & Liu, G.-J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092707 · Cited by 124 · see citing works
In Vivo TSPO Signal and Neuroinflammation in Alzheimer’s Disease
Tournier, B. B., Tsartsalis, S., Ceyzériat, K., Garibotto, V., & Millet, P. (2020) · Cells · doi:10.3390/cells9091941 · Cited by 79 · see citing works
Rivera-Escalera, F., Pinney, J. J., Owlett, L., Ahmed, H., Thakar, J., Olschowka, J. A., Elliott, M. R., & O’Banion, M. K. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1645-7 · Cited by 75 · see citing works
“TSPO is increased on activated microglia [92, 93], it is”
Brendel, M., Kleinberger, G., Probst, F., Jaworska, A., Overhoff, F., Blume, T., Albert, N. L., Carlsen, J., Lindner, S., Gildehaus, F. J., et al. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00008 · Cited by 66 · see citing works
Impact of Endothelial 18-kDa Translocator Protein on the Quantification of<sup>18</sup>F-DPA-714
Wimberley, C., Lavisse, S., Brulon, V., Peyronneau, M.-A., Leroy, C., Bodini, B., Remy, P., Stankoff, B., Buvat, I., & Bottlaender, M. (2018) · Journal of Nuclear Medicine · doi:10.2967/jnumed.117.195396 · Cited by 63 · see citing works
Colon-Perez, L. M., Ibanez, K. R., Suarez, M., Torroella, K., Acuna, K., Ofori, E., Levites, Y., Vaillancourt, D. E., Golde, T. E., Chakrabarty, P., et al. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.116138 · Cited by 41 · see citing works
Neuroimaging of mouse models of Alzheimer’s disease
Jullienne, A., Trinh, M. V., & Obenaus, A. (2022) · Biomedicines · doi:10.3390/biomedicines10020305 · Cited by 32 · see citing works
- Authors
- Mirzaei, N., Tang, S. P., Ashworth, S., Coello, C., Plisson, C., Passchier, J., Selvaraj, V., Tyacke, R. J., Nutt, D. J., & Sastre, M.
- Affiliations
- Imperial College London (GB)
- Imanova Limited Du Cane Road London W12 0NN United Kingdom
- Cornell University (US)
- Corresponding author
- Tyacke, Robin J.
- Sastre, Magdalena
- ORCID
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2016-03-09
- Volume
- 64
- Issue
- 6
- Pages
- 993-1006
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2294606443
- Semantic Scholar
- e0c913f10135234b884300c05eb5b83fbd1af6e0
- Cited by
- 82
- References
- 83
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 12 · 2021: 10 · 2020: 9 · 2019: 12 · 2018: 11 · 2017: 13 · 2016: 3
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
- Funders
- Alzheimer’s Research UK (ARUK‐PPG2012B‐21)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- microglial activation, Alzheimer's disease, [11C]PBR28, translocator protein (TSPO), 5xFAD mice, positron emission tomography, amyloid deposits, Iba1, radioligand binding, hippocampus
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Brain, Disease Models, Animal, Mice, Transgenic, Microglia, Receptors, GABA, Positron-Emission Tomography, Mice
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.
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