In Vivo Assessment of Neuroinflammation in 4‐Repeat Tauopathies
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Abstract
Background: Neuroinflammation has received growing interest as a therapeutic target in neurodegenerative disorders, including 4‐repeat tauopathies. Objectives: The aim of this cross‐sectional study was to investigate 18 kDa translocator protein positron emission tomography (PET) as a biomarker for microglial activation in the 4‐repeat tauopathies corticobasal degeneration and progressive supranuclear palsy. Methods: Specific binding of the 18 kDa translocator protein tracer 18 F‐GE‐180 was determined by serial PET during pharmacological depletion of microglia in a 4‐repeat tau mouse model. The 18 kDa translocator protein PET was performed in 30 patients with corticobasal syndrome (68 ± 9 years, 16 women) and 14 patients with progressive supranuclear palsy (69 ± 9 years, 8 women), and 13 control subjects (70 ± 7 years, 7 women). Group comparisons and associations with parameters of disease progression were assessed by region‐based and voxel‐wise analyses. Results: Tracer binding was significantly reduced after pharmacological depletion of microglia in 4‐repeat tau mice. Elevated 18 kDa translocator protein labeling was observed in the subcortical brain areas of patients with corticobasal syndrome and progressive supranuclear palsy when compared with controls and was most pronounced in the globus pallidus internus, whereas only patients with corticobasal syndrome showed additionally elevated tracer binding in motor and supplemental motor areas. The 18 kDa translocator protein labeling was not correlated with parameters of disease progression in corticobasal syndrome and progressive supranuclear palsy but allowed sensitive detection in patients with 4‐repeat tauopathies by a multiregion classifier. Conclusions: Our data indicate that 18 F‐GE‐180 PET detects microglial activation in the brain of patients with 4‐repeat tauopathy, fitting to predilection sites of the phenotype. The 18 kDa translocator protein PET has a potential for monitoring neuroinflammation in 4‐repeat tauopathies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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Using another TSPO tracer 18F-GE-180, elevated TSPO uptake was observed in subcortical brain regions, especially in the medial pallidus in PSP.
“Using another TSPO tracer 18F-GE-180, elevated TSPO uptake was also observed in subcortical brain regions, especially in the medial pallidus in PSP.377”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [377]
Microglial activation in PSP brains was also detected by PET imaging.
“Microglial activation in PSP brains was also detected by PET imaging.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [377]
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Larrea, A., Elexpe, A., Díez-Martín, E., Torrecilla, M., Astigarraga, E., & Barreda‐Gómez, G. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45110539 · Cited by 21 · see citing works
Respondek, G., & Höglinger, G. U. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.644064 · Cited by 18 · see citing works
Self-citationPalleis, C., Franzmeier, N., Weidinger, E., Bernhardt, A. M., Katzdobler, S., Wall, S., Ferschmann, C., Harris, S., Schmitt, J., Schuster, S., et al. (2023) · Neurology · doi:10.1212/wnl.0000000000207901 · Cited by 18 · see citing works
Self-citationPET Imaging to Measure Neuroinflammation In Vivo
Malpetti, M., Franzmeier, N., & Brendel, M. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-3774-6_12 · Cited by 14 · see citing works
Self-citationMuñoz‐Delgado, L., Luque-Ambrosiani, A. C., Zamora, B. B., Macías‐García, D., Jesús, S., Adarmes-Gómez, A. D., Ojeda‐Lepe, E., Carrillo, F., & Mir, P. (2024) · European Journal of Neurology · doi:10.1111/ene.16451 · Cited by 14 · see citing works
Positron Emission Tomography in Animal Models of Tauopathies
Cao, L., Kong, Y., Ji, B., Ren, Y., Guan, Y., & Ni, R. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.761913 · Cited by 14 · see citing works
Multi-omics and 3D-imaging reveal bone heterogeneity and unique calvaria cells in neuroinflammationPreprint
Kolabas, Z. I., Kuemmerle, L. B., Perneczky, R., Förstera, B., Büttner, M., Çalışkan, Ö. Ş., Ali, M., Rong, Z., Mai, H., Hummel, S., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.12.24.473988 · Cited by 13 · see citing works
Self-citationKaniuk, J. K., Kumar, D., Mazurek, C. Y., Khavari, S., Sollenberger, C. H., Ahuja, A., Mossner, J. M., & Ahuja, C. S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26157191 · Cited by 11 · see citing works
Jellinger, K. A. (2025) · Diseases · doi:10.3390/diseases13020039 · Cited by 10 · see citing works
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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 · see citing works
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Self-citationPathomechanisms of depression in progressive supranuclear palsy
Jellinger, K. A. (2023) · Journal of Neural Transmission · doi:10.1007/s00702-023-02621-w · Cited by 7 · see citing works
Does the Anti‐Tau Strategy in Progressive Supranuclear Palsy Need to Be Reconsidered? No
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Self-citationPathomechanisms of neuropsychiatric disturbances in atypical parkinsonian disorders: a current view
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Markiewicz, M. G., Migda, B., Otto‐Ślusarczyk, D., Madetko‐Alster, N., Wiercińska‐Drapało, A., Darewicz, M., Struga, M., & Alster, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262412122 · Cited by 4 · see citing works
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Self-citationSatoh, R., Utianski, R. L., Duffy, J. R., Clark, H. M., Stephens, Y. C., Lee, J., Baker, M. C., Rademakers, R., Lowe, V. J., Josephs, K. A., et al. (2025) · Clinical Nuclear Medicine · doi:10.1097/rlu.0000000000005962 · Cited by 3 · see citing works
Using iPSC models to examine neuron–glia interactions in neurodegenerative diseases
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4-Repeat Tauopathien – Progressive Supranukleäre Blickparese und kortikobasale Degeneration
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Self-citationNeuroimaging in progressive supranuclear palsy
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Neuroinflammation Imaging in Neurodegenerative Diseases
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Fluid and Imaging Markers of Glial Reactivity
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Self-citationTransport vehicle–mediated TREM2 PET maps myeloid cells in the glioblastoma microenvironmentPreprint
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- Authors
- Palleis, C., Sauerbeck, J., Beyer, L., Harris, S., Schmitt, J., Morenas‐Rodriguez, E., Finze, A., Nitschmann, A., Ruch‐Rubinstein, F., Eckenweber, F., Biechele, G., Blume, T., Shi, Y., Weidinger, E., Prix, C., Bötzel, K., Danek, A., Rauchmann, B., Stöcklein, S., Lindner, S., Unterrainer, M., Albert, N. L., Wetzel, C., Rupprecht, R., Rominger, A., Bartenstein, P., Herms, J., Perneczky, R., Haass, C., Levin, J., Höglinger, G. U., & Brendel, M.
- Affiliations
- LMU Klinikum (DE)
- German Center for Neurodegenerative Diseases Munich Germany
- Department of Nuclear Medicine University Hospital of Munich, LMU Munich Munich Germany
- German Center for Neurodegenerative Diseases (DE)
- Department of Radiology University Hospital of Munich, LMU Munich Munich Germany
- University of Regensburg (DE)
- University of Bern (CH)
- Corresponding author
- Levin, Johannes
- Höglinger, Günter U.
- Brendel, Matthias
- ORCID
- Palleis, Carla
- Sauerbeck, Julia
- Beyer, Leonie
- Harris, Stefanie
- Schmitt, Julia
- Finze, Anika
- Nitschmann, Alexander
- Biechele, Gloria
- Shi, Yuan
- Weidinger, Endy
- Prix, Catharina
- Bötzel, Kai
- Danek, Adrian
- Rauchmann, Boris‐Stephan
- Lindner, Simon
- Unterrainer, Marcus
- Albert, Nathalie L.
- Wetzel, Christian
- Rupprecht, Rainer
- Rominger, Axel
- Bartenstein, Peter
- Herms, Jochen
- Perneczky, Robert
- Haass, Christian
- Levin, Johannes
- Höglinger, Günter U.
- Brendel, Matthias
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2020-11-27
- Volume
- 36
- Issue
- 4
- Pages
- 883-894
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- OpenAlex
- W3108185411
- Cited by
- 62
- References
- 49
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 11 · 2023: 12 · 2022: 9 · 2021: 12
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Movement Disorders (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by-nc)
- Funders
- Deutsche Forschungsgemeinschaft (421887978, 422182557, BR4580/1‐1, EXC 2145 SyNergy ‐ ID 390857198, RO5194/1‐1)
- Deutsches Zentrum für Neurodegenerative Erkrankungen (DescribePSP Study)
- NOMIS Stiftung (FTLD project)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- neuroinflammation, translocator protein (TSPO), microglial activation, corticobasal degeneration, progressive supranuclear palsy, microglial depletion, disease progression biomarkers, globus pallidus internus
- MeSH terms
- Aged, Alzheimer Disease, Animals, Brain, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Supranuclear Palsy, Progressive, tau Proteins, Tauopathies, Mice
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