Study Explores New Way to Monitor Neuroinflammation

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by Patricia Inácio, PhD |

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Overactivation of microglia cells — known to drive neuroinflammation in diseases like Parkinson’s — can be detected by measuring a panel of different proteins in the cerebrospinal fluid (CSF), the liquid that surrounds the brain and spinal cord, a study reports.

The finding supports the potential of these proteins as biomarkers in the clinic to aid in monitoring neuroinflammation stages and response to therapies in patients.

The study, “Signatures of glial activity can be detected in the CSF proteome,” was published in the journal PNAS.

Chronic inflammation in the brain (neuroinflammation) is a hallmark of Parkinson’s, Alzheimer’s and other neurodegenerative diseases.

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“Inflammatory processes in the brain are common in Alzheimer’s and Parkinson’s disease. In these processes, so-called microglial cells play an important role,” Stephan Käser, PhD, with the Hertie Institute for Clinical Brain Research and the University of Tübingen, in Germany, said in a press release. Kaser and professor Mathias Jucker, PhD also at the University of Tübingen, led the study.

Microglia cells — considered the immune cells of the brain – play important roles in nervous system immunity, protecting the brain form pathogens. However, these cells are known to become overactive during Parkinson’s, helping to drive neuroinflammation in the long-run.

“We suspect that this reaction initially has a positive effect on the course of the disease, and then turns into a negative impact later on,” Käser said.

However, research is scarce about detecting overactivation of microglial cells outside the brain, such as in the CSF.

In this study, the researchers at the University of Tübingen collaborated with researchers at the German Center for Neurodegenerative Diseases, in Munich, and measured the levels of several proteins in a tiny drop of CSF from mouse models of Alzheimer’s and Parkinson’s.

“Using state-of-the art measurement technology, we were able to measure more than 600 proteins simultaneously in just two microliters of liquor — a tiny drop of fluid,” Käser explained.

The results revealed a panel of more than 20 proteins whose levels were increased in the CSF of both animal models when compared to healthy animals, who served as controls.

“We found that the concentration of 25 proteins was altered in both mouse models compared with healthy animals of the same age,” said Käser.

These proteins previously were reported to be altered in the CSF of humans with Alzheimer’s. When assessing their origin, the researchers found most of them were produced by microglia cells.

These findings support the potential of these proteins as biomarkers of glial cell activity and, as a consequence, of the varying degrees of neuroinflammation in people with diseases like Parkinson’s.

“The ability to measure inflammatory responses in the cerebrospinal fluid would be a major advance,” said Jucker. “This would allow us to better understand different disease stages and also to test anti-inflammatory substances in clinical trials.”

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