University of Tübingen: Protein changes in the cerebrospinal fluid indicate inflammatory processes in the brain

Alzheimer’s, Parkinson’s and other neurodegenerative diseases are associated with inflammatory processes in the brain. Tübingen researchers have succeeded in identifying a group of proteins in the cerebrospinal fluid that could provide information about such inflammatory processes. As so-called biomarkers, these proteins could help in the future to better understand disease processes and to test the effect of potential drugs against these inflammations. The research team led by Stephan Käser and Professor Dr. Mathias Jucker at the Hertie Institute for Clinical Brain Research and the University of Tübingen, in collaboration with Professor Dr. Stefan Lichtenthaler from the Munich branch of the German Center for Neurodegenerative Diseases has now published his study in the specialist journal PNAS .

“Inflammation in the brain is a well-known symptom of Alzheimer’s and Parkinson’s disease,” explains Käser, who headed the study. “So-called microglia play an important role here.” As “garbage chutes”, these cells normally protect our brain from harmful pathogens and substances. In the case of a neurodegenerative disease, they are chronically active and release substances themselves. “It is assumed that this reaction of the microglia, which initially has a positive effect on the course of the disease, later turns negative,” says Käser.

In order to obtain information about the dynamic inflammatory reactions in the brain, the Tübingen research team has now searched for possible molecular biomarkers. These are substances whose presence or change in concentration in the body indicates a disease process. They can be measured in blood, urine or other body fluids and are an important tool in medical diagnostics or for observing the course of a disease.

In the current study, the neurobiologists analyzed the cerebrospinal fluid of mice that show characteristic features of Alzheimer’s disease or Parkinson’s disease. “Using modern measurement technology, we were able to measure more than 600 proteins at the same time in just two microliters of cerebrospinal fluid, i.e. a tiny drop,” reports Käser. “We found that the concentration of 25 proteins was altered in both mouse models compared to healthy animals of the same age.”

“It is remarkable that the majority of these proteins come from glial cells or can be associated with them,” the neurobiologist continues. “Practically all of them can also be detected in human cerebrospinal fluid and some of them have changed in people with Alzheimer’s.” The changed concentrations of the proteins could reflect different activation stages of the glial cells. They would therefore have the potential to serve as biomarkers.

“The possibility of measuring the inflammatory reactions in the cerebrospinal fluid would be a major advance,” explains co-author Jucker. “That would allow us to better understand the stages of the disease and also to test the first drugs against this inflammation in clinical studies.” The new findings from the laboratory would thus find practical application in patient care and would therefore be a good example of translational brain research.

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