Evidence of injury and neuroprotective processes long before the onset of dementia symptoms-ScienceDaily

In recent years, it has become clear that inflammatory processes associated with the immune system of the brain (also known as “neuroinflammation”) contribute significantly to the development of Alzheimer’s disease. With this in mind, scientists have analyzed a variety of immunological biomarkers characterized by good detectability and reproducible results in cerebrospinal fluid. “It was already known that these markers indicate immune processes in the context of Alzheimer’s disease, but how these markers relate to brain volume, cognitive performance, and other parameters is current. It wasn’t so comprehensively studied, “explains Professor Michael Heneka. , Led the current research during his many years of tenure at DZNE and UKB. Since the beginning of this year, he has been the director of the Luxembourg Center for Biomedical Sciences.

“We found that some of these inflammatory markers stand out even if we don’t have any symptoms of dementia yet,” says Heneka. “The data so far do not allow us to determine the lead time at this time, but we estimate it will take at least 10 to 20 years.”

Extensive database

The starting point for the study was data from the so-called DELCODE study, where DZNE collaborates with several university hospitals across Germany to study dementia and its preliminary stages. The current research project included findings from about 300 females and men over the age of 60. This group consisted of cognitively normal adults, individuals with varying degrees of severe memory impairment, and people with Alzheimer’s disease. Cerebrospinal fluid and standardized memory test samples were available to all study participants, and magnetic resonance imaging of the brain was obtained from most of them. The data for each study participant included a baseline examination and at least one follow-up one year later. In some subjects, the findings spanned multiple follow-ups over up to 5 years.

Blow without dementia

“Biomarkers for amyloid and tau have been established. These are proteins that accumulate in the brain of Alzheimer’s disease and can also be detected in cerebrospinal fluid. They usually change levels even before the onset of dementia symptoms. This is neuropathy. I wanted to know if inflammation markers responded as well, “said Dr. DZNE scientist and one of the first authors of the current publication of” Neuron. ” Frederic Brosseron said. “In fact, we found that most inflammation markers were elevated, especially if the markers of nerve damage were elevated. This is true even if these individuals have not yet shown symptoms of dementia. Therefore, the recorded inflammation markers are especially useful for the study of neuroinflammation. In the early stages of the disease. “

Evidence of neuroprotection

In particular, two of these markers (proteins belonging to the “TAM receptor family”) appear to be associated with injury control programs. Especially in study participants with these high marker levels, brain volume was relatively large and cognitive function slowly declined over time. To validate these findings, Heneka’s team evaluated data from a study cohort at the ACE Alzheimer Center Barcelona with more than 700 adults. This analysis confirmed that the results of the DELCODE study were correct.

“The inflammatory process is not bad in itself, especially at first it is the normal protective response of the immune system to threatening stimuli, but they should not be too long and need to be regulated,” says Heneka. increase. He explains that TAM family proteins are known to affect the immune response and promote the disposal of cellular waste. “Supporting this protective function is an interesting approach for pharmaceutical research. This is where I see the potential application of the markers we have identified. Early detection of dementia in everyday care. Because of this, the measurement of these markers is too complex. There are other technical options for drugs in clinical trials. In the study, whether the intervention is working and whether the drugs tested are effective. We need an indicator to evaluate. TAM markers can be very helpful in this. “

This study was partially supported by funding from the international PREADAPT project funded by the EU Collaborative Program-Neurodegenerative Diseases Research (JPND).