Nature Communications (Aug 2023)
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 de 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 van der 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,
- David R. Owen
Affiliations
- Erik Nutma
- Department of Pathology, Amsterdam UMC – Location VUmc
- Nurun Fancy
- Department of Brain Sciences, Imperial College London
- Maria Weinert
- Department of Brain Sciences, Imperial College London
- Stergios Tsartsalis
- Department of Brain Sciences, Imperial College London
- Manuel C. Marzin
- Department of Pathology, Amsterdam UMC – Location VUmc
- Robert C. J. Muirhead
- Department of Brain Sciences, Imperial College London
- Irene Falk
- Viral Immunology Section, NIH
- Marjolein Breur
- Department of Pathology, Amsterdam UMC – Location VUmc
- Joy de Bruin
- Department of Pathology, Amsterdam UMC – Location VUmc
- David Hollaus
- Department of Pathology, Amsterdam UMC – Location VUmc
- Robin Pieterman
- Department of Pathology, Amsterdam UMC – Location VUmc
- Jasper Anink
- Department of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience
- David Story
- UK Dementia Research Institute at Edinburgh
- Siddharthan Chandran
- UK Dementia Research Institute at Edinburgh
- Jiabin Tang
- Department of Brain Sciences, Imperial College London
- Maria C. Trolese
- Department of Neuroscience, Mario Negri Institute for Pharmacological Research IRCCS
- Takashi Saito
- Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute
- Takaomi C. Saido
- Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University
- Katharine H. Wiltshire
- Department of Brain Sciences, Imperial College London
- Paula Beltran-Lobo
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Alexandra Phillips
- Department of Brain Sciences, Imperial College London
- Jack Antel
- Montreal Neurological Institute, McGill University
- Luke Healy
- Montreal Neurological Institute, McGill University
- Marie-France Dorion
- Division of Biomedical Sciences, Memorial University of Newfoundland
- Dylan A. Galloway
- Division of Biomedical Sciences, Memorial University of Newfoundland
- Rochelle Y. Benoit
- Division of Biomedical Sciences, Memorial University of Newfoundland
- Quentin Amossé
- Department of Psychiatry, University of Geneva
- Kelly Ceyzériat
- Department of Psychiatry, University of Geneva
- Aurélien M. Badina
- Department of Psychiatry, University of Geneva
- Enikö Kövari
- Department of Psychiatry, University of Geneva
- Caterina Bendotti
- Department of Neuroscience, Mario Negri Institute for Pharmacological Research IRCCS
- Eleonora Aronica
- Department of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience
- Carola I. Radulescu
- Department of Brain Sciences, Imperial College London
- Jia Hui Wong
- Neurobiology of Aging and Disease Laboratory, Lee Kong Chian School of Medicine, Nanyang Technological University Singapore
- Anna M. Barron
- Neurobiology of Aging and Disease Laboratory, Lee Kong Chian School of Medicine, Nanyang Technological University Singapore
- Amy M. Smith
- UK Dementia Research Institute at Imperial College London
- Samuel J. Barnes
- Department of Brain Sciences, Imperial College London
- David W. Hampton
- UK Dementia Research Institute at Edinburgh
- Paul van der Valk
- Department of Pathology, Amsterdam UMC – Location VUmc
- Steven Jacobson
- Viral Immunology Section, NIH
- Owain W. Howell
- Institute of Life Science (ILS), Swansea University Medical School
- David Baker
- Department of Neuroscience and Trauma, Blizard Institute, Queen Mary University of London
- Markus Kipp
- Institute of Anatomy, Rostock University Medical Center
- Hannes Kaddatz
- Institute of Anatomy, Rostock University Medical Center
- Benjamin B. Tournier
- Department of Psychiatry, University of Geneva
- Philippe Millet
- Department of Psychiatry, University of Geneva
- Paul M. Matthews
- Department of Brain Sciences, Imperial College London
- Craig S. Moore
- Division of Biomedical Sciences, Memorial University of Newfoundland
- Sandra Amor
- Department of Pathology, Amsterdam UMC – Location VUmc
- David R. Owen
- Department of Brain Sciences, Imperial College London
- DOI
- https://doi.org/10.1038/s41467-023-40937-z
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 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.
