Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

Erik Nutma, Nurun Fancy, Maria Weinert, Stergios Tsartsalis, Manuel C. Marzin, Robert C. J. Muirhead, Irene Falk, Marjolein Breur, Joy Bruin, David Hollaus, Robin Pieterman, Jasper Anink, David Story, Siddharthan Chandran, Jiabin Tang, Maria C. Trolese, Takashi Saito, Takaomi C. Saido, Katharine H. Wiltshire, Paula Beltran-Lobo, Alexandra Phillips, Jack Antel, Luke Healy, Marie-France Dorion, Dylan A. Galloway, Rochelle Y. Benoit, Quentin Amossé, Kelly Ceyzériat, Aurélien M. Badina, Enikö Kövari, Caterina Bendotti, Eleonora Aronica, Carola I. Radulescu, Jia Hui Wong, Anna M. Barron, Amy M. Smith, Samuel J. Barnes, David W. Hampton, Paul Valk, Steven Jacobson, Owain W. Howell, David Baker, Markus Kipp, Hannes Kaddatz, Benjamin B. Tournier, Philippe Millet, Paul M. Matthews, Craig S. Moore, Sandra Amor () and David R. Owen ()
Additional contact information
Erik Nutma: Amsterdam UMC – Location VUmc
Nurun Fancy: Imperial College London
Maria Weinert: Imperial College London
Stergios Tsartsalis: Imperial College London
Manuel C. Marzin: Amsterdam UMC – Location VUmc
Robert C. J. Muirhead: Imperial College London
Irene Falk: Viral Immunology Section, NIH
Marjolein Breur: Amsterdam UMC – Location VUmc
Joy Bruin: Amsterdam UMC – Location VUmc
David Hollaus: Amsterdam UMC – Location VUmc
Robin Pieterman: Amsterdam UMC – Location VUmc
Jasper Anink: University of Amsterdam, Amsterdam Neuroscience
David Story: UK Dementia Research Institute at Edinburgh
Siddharthan Chandran: UK Dementia Research Institute at Edinburgh
Jiabin Tang: Imperial College London
Maria C. Trolese: Mario Negri Institute for Pharmacological Research IRCCS
Takashi Saito: RIKEN Brain Science Institute
Takaomi C. Saido: Institute of Brain Science, Nagoya City University
Katharine H. Wiltshire: Imperial College London
Paula Beltran-Lobo: King’s College London
Alexandra Phillips: Imperial College London
Jack Antel: McGill University
Luke Healy: McGill University
Marie-France Dorion: Memorial University of Newfoundland
Dylan A. Galloway: Memorial University of Newfoundland
Rochelle Y. Benoit: Memorial University of Newfoundland
Quentin Amossé: University of Geneva
Kelly Ceyzériat: University of Geneva
Aurélien M. Badina: University of Geneva
Enikö Kövari: University of Geneva
Caterina Bendotti: Mario Negri Institute for Pharmacological Research IRCCS
Eleonora Aronica: University of Amsterdam, Amsterdam Neuroscience
Carola I. Radulescu: Imperial College London
Jia Hui Wong: Nanyang Technological University Singapore
Anna M. Barron: Nanyang Technological University Singapore
Amy M. Smith: UK Dementia Research Institute at Imperial College London
Samuel J. Barnes: Imperial College London
David W. Hampton: UK Dementia Research Institute at Edinburgh
Paul Valk: Amsterdam UMC – Location VUmc
Steven Jacobson: Viral Immunology Section, NIH
Owain W. Howell: Swansea University Medical School
David Baker: Blizard Institute, Queen Mary University of London
Markus Kipp: Rostock University Medical Center
Hannes Kaddatz: Rostock University Medical Center
Benjamin B. Tournier: University of Geneva
Philippe Millet: University of Geneva
Paul M. Matthews: Imperial College London
Craig S. Moore: Memorial University of Newfoundland
Sandra Amor: Amsterdam UMC – Location VUmc
David R. Owen: Imperial College London

Nature Communications, 2023, vol. 14, issue 1, 1-25

Abstract: Abstract Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.

Date: 2023
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DOI: 10.1038/s41467-023-40937-z

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