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-LoboAlexandra 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)5247
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - 28 Aug 2023

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Mice
  • Microglia
  • Neurodegenerative Diseases/genetics
  • Macrophages
  • Myeloid Cells
  • Genetic Drift

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