Neuroinflammation can lead to serious neurological or psychiatric diseases, for which there is presently one biomarker available for medical imaging to visualise cerebral inflammation. Trouble is, it has been unclear how to interpret this biomarker. Researchers have now found that a large quantity of this protein indicates a large quantity of inflammatory cells, but its presence is not a sign of their overactivation. These results, published in Nature Communications, pave the way for optimal observation of neuroinflammatory processes with other potential biomarkers, and a re-evaluation of prior research.
In the brain, microglial cells play an important role in inflammation and its potential overactivation. They can be ”activated” when dysfunction occurs, phagocytise pathological cells or proteins and even produce protective substances. Currently, in medical imaging, only one marker can be used to locate and measure microglia non-invasively and in vivo: the TSPO protein, which is present in these cells. This protein can be observed by Positron Emission Tomography (PET), a common imaging technique.
A TSPO of insight
”Hundreds of studies have used PET scans of this protein to explore and quantify microglia. However, no study has succeeded in precisely interpreting the significance of its quantity in the context of an inflammatory reaction,” explains Stergios Tsartsalis, senior clinical associate in the Department of Psychiatry at the UNIGE Faculty of Medicine. Together with other researchers, Stergios Tsartsalis sought to determine if a large quantity of TSPO correspond to a large quantity of inflammatory cells, and whether it is a sign of their overactivation.
The international research team worked on the brains of mouse models of Alzheimer’s disease, amyotrophic lateral sclerosis and multiple sclerosis, and on post-mortem brain samples from patients affected by the same diseases. ”We discovered that a high density of TSPO protein is indeed an indicator of a high density of microglia. On the other hand, the observation of TSPO does not allow us to say whether or not the inflammatory cells are overactivated,” explains the UNIGE researcher, co-first author of the study.
Re-reading the past, optimising the future
This discovery highlights the value of medical imaging of TSPO: it makes it possible to identify cases where the neuroinflammatory disease is linked to a deregulation in the number of glial cells. In addition, the scientists have identified two markers of the state of microglia activation in humans – the LCP2 and TFEC proteins – setting the stage for new medical imaging approaches.
”These results represent a further step towards understanding the role of microglia in neuroinflammation. They will help to optimise the focus of future studies and also to review the conclusions of previous research,” enthuses Stergios Tsartsalis.
Source: Université de Genève
