Prospects and challenges of imaging neuroinflammation beyond TSPO in Alzheimer’s disease
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Neuroinflammation, as defined by the activation of microglia and astrocytes, has emerged in the last years as a key element of the pathogenesis of neurodegenerative diseases based on genetic findings and preclinical and human studies. This has raised the need for new methodologies to assess and follow glial activation in patients, prompting the development of PET ligands for molecular imaging of glial cells and novel structural MRI and DTI tools leading to a multimodal approach. The present review describes the recent advancements in microglia and astrocyte biology in the context of health, ageing, and Alzheimer's disease, the most common dementia worldwide. The review further delves in molecular imaging discussing the challenges associated with past and present targets, including conflicting findings, and finally, presenting novel methodologies currently explored to improve our in vivo knowledge of the neuroinflammatory patterns in Alzheimer's disease. With glial cell activation as a potential therapeutic target in neurodegenerative diseases, the translational research between cell biologists, chemists, physicists, radiologists, and neurologists should be strengthened.
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PET imaging can show neuroinflammatory parameters in the brain in vivo.
“This technique can show neuroinflammatory parameters in the brain in vivo [508].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [508]
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Peripheral and central immune system crosstalk in Alzheimer disease — a research prospectus
Bettcher, B. M., Tansey, M. G., Dorothée, G., & Heneka, M. T. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00549-x · Cited by 427 · see citing works
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Self-citationGlial Cell-Mediated Neuroinflammation in Alzheimer’s Disease
Al-Ghraiybah, N. F., Wang, J., Alkhalifa, A. E., Roberts, A. B., Raj, R., Yang, E., & Kaddoumi, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810572 · Cited by 204 · see citing works
Microglia and Astrocyte Function and Communication: What Do We Know in Humans?
Garland, E. F., Hartnell, I. J., & Boche, D. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.824888 · Cited by 165 · see citing works
“, 2019), suggesting that the reduced metabolism in disease may be related to astrocyte degeneration (Boche et al., 2019).”
BackgroundSelf-citationMalko, P., Jia, X., Wood, I., & Jiang, L. (2022) · Glia · doi:10.1002/glia.24311 · Cited by 110 · see citing works
“…generation in primary mouse microglial cells Differing from BV2 cells, primary microglial cells under in vitro culture conditions, as observed in vivo, for example, in the brain (Boche et al., 2019), exhibit a dynamic range of morphologies, which are asso- ciated with their functional states.”
BackgroundA microengineered Brain-Chip to model neuroinflammation in humans
Pediaditakis, I., Kodella, K. R., Manatakis, D. V., Le, C. Y., Barthakur, S., Sorets, A. G., Gravanis, A., Ewart, L. C., Rubin, L. L., Manolakos, E. S., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104813 · Cited by 84 · see citing works
“…by significant increases in CD68 positive cells or the proportion of GFAP-positive cells respectively (Figures 4E to 4H and S3B, S3C), recapitulating in vivo findings for glial cells that constitute the first response to inflammatory and infectious stimuli (Boche et al., 2019; Sun et al., 2008).”
BackgroundNeuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy
Malpetti, M., Passamonti, L., Rittman, T., Jones, P. S., Vázquez Rodríguez, P., Bevan‐Jones, W. R., Hong, Y. T., Fryer, T. D., Aigbirhio, F. I., O'Brien, J. T., et al. (2020) · Annals of Neurology · doi:10.1002/ana.25911 · Cited by 83 · see citing works
Neuroinflammation predicts disease progression in progressive supranuclear palsy
Malpetti, M., Passamonti, L., Jones, P. S., Street, D., Rittman, T., Fryer, T. D., Hong, Y. T., Vàsquez Rodriguez, P., Bevan-Jones, W. R., Aigbirhio, F. I., et al. (2021) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-325549 · Cited by 85 · see citing works
Neuroinflammation PET imaging of the translocator protein (TSPO) in Alzheimer's disease: An update
Gouilly, D., Saint‐Aubert, L., Ribeiro, M. J., Salabert, A., Tauber, C., Péran, P., Arlicot, N., Pariente, J., & Payoux, P. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15613 · Cited by 66 · see citing works
“Although the development of PET tracers to explore neuroinflammation is rapidly evolving (Boche et al., 2019), the translocator protein (TSPO) remains the most common target used in neurological diseases (Kreisl et al., 2020).”
BackgroundImaging of Reactive Astrogliosis by Positron Emission Tomography
Harada, R., Furumoto, S., Kudo, Y., Yanai, K., Villemagne, V. L., & Okamura, N. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.807435 · Cited by 63 · see citing works
“These findings suggest that a more specific and selective targets beyond TSPO are required for PET imaging of activated glial cells (Boche et al., 2019; Jain et al., 2020).”
BackgroundInflammation in dementia with Lewy bodies
Amin, J., Erskine, D., Donaghy, P. C., Surendranathan, A., Swann, P., Kunicki, A., Boche, D., Holmes, C., McKeith, I. G., O'Brien, J. T., et al. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105698 · Cited by 62 · see citing works
“Novel PET ligands are in development that bind to other potential microglial sites or to astrocytes (Boche et al., 2019).”
Self-citationThe Immune System's Role in the Consequences of Mild Traumatic Brain Injury (Concussion)
Verboon, L. N., Patel, H. C., & Greenhalgh, A. D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.620698 · Cited by 58 · see citing works
Picker, L. D., Victoriano, G. M., Richards, R., Gorvett, A. J., Lyons, S., Buckland, G. R., Tofani, T., Norman, J. L., Chatelet, D. S., Nicoll, J. A. R., et al. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.07.017 · Cited by 56 · see citing works
“While in vivo PET neuroimaging has the advantage of allowing longitudinal study of the dynamics of glial activation, inconsistent results among cross-sectional PET studies have raised questions about the validity of the TSPO tracer as biomarker and the potential role of immunosenescence and symptomatic state on microg…”
BackgroundResultSelf-citationMolecular Imaging Approaches in Dementia.
Villemagne, V., Barkhof, F., Garibotto, V., Landau, S., Nordberg, A., & van Berckel, B. N. (2021) · Radiology · doi:10.1148/radiol.2020200028 · Cited by 41 · see citing works
Singh, P., Adhikari, A., Singh, D., Gond, C., & Tiwari, A. K. (2022) · ACS Omega · doi:10.1021/acsomega.2c00588 · Cited by 47 · see citing works
Salvadó, G., Shekari, M., Falcón, C., Operto, G., Milà‐Alomà, M., Sánchez‐Benavides, G., Cacciaglia, R., Arenaza‐Urquijo, E. M., Niñerola‐Baizán, A., Perissinotti, A., et al. (2022) · Brain Communications · doi:10.1093/braincomms/fcac134 · Cited by 45 · see citing works
“PET tracers targeting microglial and astroglial activation, like those binding to translocator protein 18 kDa (TSPO) or monoamine oxidase B (MAO-B), may also help us to decipher these underlying mechanisms in the near future.(33) Finally another hypothesis that cannot be disregarded is that these differences might be…”
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“In addition, new tracers for imaging neuroinflammation beyond TSPO are under development for microgliosis [79, 80] and astrogliosis [4] (including novel MAO-B tracer [81]).”
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- Authors
- Faculty, O. B. O. T. M., Boche, D., Gerhard, A., & Rodriguez-Vieitez, E.
- Affiliations
- University of Southampton (GB)
- University of Manchester (GB)
- Corresponding author
- Boche, Delphine
- Venue
- European Journal of Nuclear Medicine and Molecular Imaging
- Published
- 2019-08-08
- Volume
- 46
- Issue
- 13
- Pages
- 2831-2847
- ISSN
- 1619-7070 (ISSN-L)
- 1619-7089
- PMC
- PMC6879435
- OpenAlex
- W2969179597
- Cited by
- 55
- References
- 144
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 7 · 2022: 14 · 2021: 14 · 2020: 6 · 2019: 3
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- Funders
- University of Southampton
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- neuroinflammation, Alzheimer's disease, microglia, astrocytes, glial activation, PET ligands, molecular imaging, multimodal imaging, diffusion tensor imaging, neurodegenerative diseases, therapeutic target
- MeSH terms
- Alzheimer Disease, Astrocytes, Humans, Inflammation, Receptors, GABA, Neuroimaging, Cognitive Dysfunction
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