Brain Health: March/April 2022

Inflammatory Markers Indicate Dementia Decades Before Symptoms Start

Steve Fink

March 2, 2022 ( — The brain’s immune system shows increased activity long before the beginning of dementia. A new study suggests that inflammatory markers, part of the body’s defense strategy against the disease, are noticeable ten to twenty years in advance.

For the study, researchers from the German Center for Neurodegenerative Diseases (DZNE) and the University Hospital Bonn (UKB) in Germany measured proteins in the cerebrospinal fluid. This is a liquid found in the brain and spinal cord, which make up the central nervous system. There, the proteins acted as biomarkers — indicators of inflammatory processes of the nervous system.

We have found that some of these inflammatory markers are conspicuous even when there are no symptoms of dementia yet. Based on the data we have so far, we can’t specify the lead time at this point. But my estimate is that it is at least ten to twenty years,” says study co-author Michael Heneka, who led the study, in a statement.

Earlier research has shown that inflammation related to the brain’s immune system, so-called neuroinflammation, adds to the development of Alzheimer’s disease, so the researchers thoroughly investigated these biomarkers for the study. “It was already known that these markers indicate immune processes in the context of Alzheimer’s disease. However, how these markers relate to brain volume, cognitive performance, and other parameters had not been studied as comprehensively as we have now,” explains Heneka.

“There are established biomarkers for amyloid and tau. These are proteins that accumulate in the brain in Alzheimer’s disease and can also be detected in the cerebrospinal fluid,” adds the study’s first author Dr. Frederic Brosseron, a scientist at DZNE. “Their levels usually change even before symptoms of dementia arise, which is considered a sign of processes for neuronal damage. We wanted to know whether inflammatory markers respond in a similar way.”

The answer turned out to be yes: “In fact, we found that most inflammatory markers are elevated, especially when a marker for neuronal damage is elevated. This applies even when these individuals do not yet show symptoms of dementia. Thus, the inflammatory markers we recorded are particularly useful for studying neuroinflammation at early stages of disease,” Dr. Brosseron continued.

Two inflammatory markers, TAM markers, appear to be part of the body’s defense system against Alzheimer’s. Study participants with high TAM levels had a larger brain volume and suffered slower cognitive decline. “Inflammatory processes are not bad per se, but rather a normal, protective reaction of the immune system to threatening stimuli, especially at the beginning. But they should not last too long, therefore they need to be regulated,” says. Heneka.

This early “damage control program” of the body could also prove useful for developing new treatments for the condition. “Supporting this protective function would be an interesting approach for pharmaceutical research. This is where I see potential for application of the markers we have identified,” adds Prof. Heneka. “For the early detection of dementia in routine care, measuring these markers is too complex. But when testing new drugs in clinical trials, there are other technical options. In trials, indicators are needed to assess whether interventions are working and whether tested drugs are effective. The TAM markers could be very useful for this.”

The study is published in the scientific journal Neuron.


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