The protein medin is deposited in the blood vessels of the brain of patients with Alzheimer’s disease together with the protein amyloid-β. DZNE researchers discovered this so-called co-aggregation. They have now published their observation in the journal Nature. “Medina has been known for more than 20 years, but its influence on diseases was previously underestimated. We were able to show that the pathological changes in the blood vessels of patients with Alzheimer’s disease are considerably improved by medina,” explains Dr. Jonas Neher from the Tübingen site. of DZNE, who conducted the study. The Hertie Institute for Clinical Brain Research in Tübingen, the University of Tübingen and several international institutions and cooperation partners were also involved in this long-term project.
Medin belongs to the amyloid group. Among these proteins, amyloid-β is best known because it clumps together in the brains of patients with Alzheimer’s disease. These aggregates then deposit both in the form of so-called plaques directly in the brain tissue, but also in its blood vessels, thus damaging the nerve cells and blood vessels respectively. But while many studies have focused on amyloid-β, medina has not garnered interest. “There was little evidence of pathology, that is, of a clinically striking finding associated with medina – and this is often the prerequisite for further study of an amyloid,” says Jonas Neher .
However, medina is actually found in the blood vessels of almost everyone over the age of 50, making it the most well-known amyloid. Jonas Neher and his team initially found that medina develops even in aging mice, and reported this finding two years ago in the scientific journal PNAS. The older the mice get, the more medina accumulates in the blood vessels of their brains, it was discovered at the time. Additionally, when the brain becomes active and triggers an increase in blood supply, vessels with deposits of medina expand more slowly than those without medina. This ability of blood vessels to expand is important, however, to provide the brain with optimal oxygen and nutrients.
For their latest findings, the researchers built on this foundation and looked specifically at Alzheimer’s disease. First, they were able to show in Alzheimer’s mouse models that medina accumulates even more strongly in brain blood vessels if amyloid-β deposits are also present. Importantly, these results were confirmed when analyzing brain tissue from organ donors with Alzheimer’s disease. However, when mice were genetically engineered to prevent medin formation, significantly fewer amyloid-β deposits developed and, therefore, less blood vessel damage occurred.
“There are only a handful of research groups in the world working on medicine,” says Jonas Neher. More recently, an American study reported that medina levels may increase in patients with Alzheimer’s disease. However, it remained unclear whether this increase is simply a consequence of the disease or if it is one of the causes. “We have now been able to show through numerous experiments that medina actually promotes vascular pathology in Alzheimer’s models,” Neher said. Thus, medina deposits are indeed a cause of damage to blood vessels. “And that indicates that medin is one of the causes of the disease,” Neher said.
In their studies, the researchers stained tissue sections from mice and patients with Alzheimer’s disease in such a way that specific proteins became visible. This allowed them to show that medina and amyloid-β are deposited together in the blood vessels of the brain – co-localization is the technical term for this. In a next step, they were able to prove that these two amyloids also co-aggregate, ie form mixed deposits. “Amazingly, medin directly interacts with amyloid-β and promotes its aggregation – this was completely unknown,” Jonas Neher summarizes the results.
It is precisely from this idea that researchers draw hope for the development of a new treatment. “Medin might be a therapeutic target for preventing vascular damage and cognitive decline resulting from amyloid accumulation in brain blood vessels,” they conclude. It is undisputed among experts that in addition to amyloid-β aggregates in brain tissue, the development of Alzheimer’s disease is also promoted by vascular alterations, i.e. reduced function or damage to blood vessels. Therefore, treatments that target not only the plaques but also the affected blood vessels might help patients.
In a next step, it will now be a question of determining whether the medina aggregates can be eliminated therapeutically and whether this intervention really has an effect on cognitive performance. The scientists first want to test this in mouse models, as these reflect pathological changes in Alzheimer’s patients very well.
