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


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. © 2023. Springer Nature Limited.

Authors Nutma E, Fancy N, Weinert M, Tsartsalis S, Marzin MC, Muirhead RCJ, Falk I, Breur M, de Bruin J, Hollaus D, Pieterman R, Anink J, Story D, Chandran S, Tang J, Trolese MC, Saito T, Saido TC, Wiltshire KH, Beltran-Lobo P, Phillips A, Antel J, Healy L, Dorion MF, Galloway DA, Benoit RY, Amossé Q, Ceyzériat K, Badina AM, Kövari E, Bendotti C, Aronica E, Radulescu CI, Wong JH, Barron AM, Smith AM, Barnes SJ, Hampton DW, van der Valk P, Jacobson S, Howell OW, Baker D, Kipp M, Kaddatz H, Tournier BB, Millet P, Matthews PM, Moore CS, Amor S, Owen DR
Journal Nature communications
Publication Date 2023 Aug 28;14(1):5247
PubMed 37640701
PubMed Central PMC10462763
DOI 10.1038/s41467-023-40937-z

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