Microglial activation plays central roles in neuro-inflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. For the first time, we show that TSPO gene and protein expression increases in activated microglia in mouse brain disease models postmortem, but does not change in a non-human primate (Callithrix jacchus) disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter that may be responsible for this, which is consistent with the hypothesis that the increase in TSPO in activated myeloid cells is unique to a subset of species within the Muroidea superfamily of rodents. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO PET reflects density of inflammatory cells rather than their activation state.
