New starting point for Alzheimer's disease therapy discovered
Mario Petrov
Researchers at the German Center for Neurodegenerative Diseases have discovered a link between the protein medin and Alzheimer’s disease.
In the blood vessels of the brains of Alzheimer’s patients, the protein medin is deposited together with the protein amyloid-β. This so-called co-aggregation was discovered by researchers at the German Center for Neurodegenerative Diseases (DZNE). They have published their findings in the popular Nature magazine. “Although medin has been known for about 20 years, its influence on disease has been underestimated until now. We have been able to show that pathological changes in the blood vessels of Alzheimer’s patients are significantly enhanced by the presence of the protein medin,” says study director Dr Jonas Neher of the German Center for Neurodegenerative Diseases in Tübingen. The Herty Institute for Clinical Brain Research in Tübingen, Tübingen University and several international institutions and partners are also involved in the long-term study.
What is medin?
Medin belongs to the amyloid group. Amyloid-β is best known of these proteins because it ‘clumps’ together in the brains of Alzheimer’s patients. These aggregates are then deposited by forming so-called plaques both directly in brain tissue and in blood vessels and thus damage nerve cells or blood vessels. Therefore, while many studies have dealt with amyloid-β, medin has not been the focus until now. “There has been little evidence of pathology, i.e. a clinically detectable finding in association with medin – and this is often a prerequisite for a more detailed study of this amyloid,” Jonas Neher explains.
In fact, medin is found in the blood vessels of almost every person over the age of 50, making it the most common known amyloid. Jonas Neher and his team initially determined that medin even develops in aging mice and reported this discovery two years ago in the scientific journal PNAS. Moreover, in the blood vessels of the brains of mice, the more medin accumulates, the older they get – that was the finding at the time. AND: when the brain becomes active and needs more blood supply, vessels filled with deposits of medin dilate more slowly than those without medin. However, this ability to expand is important for the optimal supply of oxygen and nutrients to the brain.
What role does medin play in Alzheimer's disease?
To arrive at their latest results, researchers use this as a starting point, looking specifically at Alzheimer’s disease. Using mouse models of Alzheimer’s disease, they were first able to show that medin accumulates even more in the blood vessels of the brain if amyloid-β deposits are present there. Corresponding findings can also be found in brain tissue of organ donors with Alzheimer’s disease. However, if mice are genetically modified in such a way that medin cannot form, there is significantly less amyloid-β deposition and thus significantly less blood vessel damage.
“There are only a handful of working groups in the world working on medin,” says Jonas Neher. A previous study from the US recently described that the median level increases in Alzheimer’s patients. However, it remains unclear whether this is simply a result of the disease or one of the causes. “We have already been able to show in many experiments that medin contributes to vascular pathology in Alzheimer’s models,” says Neher. Hence, deposits of medin are actually the cause of blood vessel damage. “And this is an indication that it contributes to the disease,” Neher adds.
How can this be used to treat the disease?
In their studies, the researchers stained tissue sections from both mice and Alzheimer’s patients in such a way that certain proteins became visible. This enabled them to show that medin and amyloid-β are deposited together in the blood vessels of the brain – the term for this is co-aggregation. With further experiments, the scientists were able to prove that these two amyloids also aggregate together – i.e. form mixed accumulations. “Surprisingly, medin interacts directly with amyloid-β and promotes its aggregation – this was completely unknown,” Jonas Neher said, summarising the outcome of the experiments.
Researchers hope that based on this outcome possible treatment can be developed. They conclude that “medin could be a therapeutic target to prevent vascular damage and cognitive deterioration resulting from amyloid accumulations in the blood vessels of the brain”. In expert circles, it is undisputed that the causes of Alzheimer’s disease are not only amyloid-β deposits in brain tissue, but also vascular changes – i.e. reduced function or damage to blood vessels. If not only the plaques are used as a target during treatment, but also the affected blood vessels, this can help patients.
It should be clarified whether the already formed medin plaques can be removed therapeutically and whether this intervention actually has an impact on memory performance. Scientists initially want to test this in mouse models because they reflect the pathological changes in Alzheimer’s patients very well.
