Come on Researchers at the German Center for Neurodegenerative Diseases have found that the Medin protein is deposited together with the amyloid beta protein in the blood vessels of the brain of Alzheimer’s patients, so that this accumulation could constitute a new target for Alzheimer’s therapies.
They have now published their observation in the journal Nature. “The medina has been known for more than 20 years, but before that its influence on diseases was underestimated. We were able to show pathological changes in the blood vessels of Alzheimer’s patients are significantly potentiated by the protein», says Dr. Jonas Neher, who led the study. The Hertie Institute for Clinical Brain Research in Tübingen (Germany), the University of Tübingen and several international institutions and cooperation partners were also involved in this long-term project.
The Medin protein belongs to the group of amyloids. Of these proteins, amyloid is best known for clumping together in the brains of Alzheimer’s patients. These aggregates are then deposited as so-called plaques directly in the brain tissue, but also in its blood vessels, thus damaging nerve cells and blood vessels.
But while many studies have focused on amyloid beta, the medina has not been the focus of attention. «There was little pathological evidence, iea clinically conspicuous finding in connection with the medina, and that is usually the prerequisite for a more in-depth investigation of an amyloid,” explains Neher.
However, Medin is found in the blood vessels of almost everyone over the age of 50, making it the most common amyloid known. Jonas Neher and his team originally discovered that Medina also develops in aging mice and reported on it two years ago in the scientific journal PNAS.
They found that the older the mice get, the more Medin accumulates in the blood vessels in their brains. In addition, when the brain is activated and causing an increased blood supply, vessels with medin deposits dilate more slowly than those without medin. However, this ability of the blood vessels to expand is important in order to optimally supply the brain with 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 mouse models of Alzheimer’s that Medin continues to accumulate in the blood vessels of the brain when amyloid beta deposits are also present. Most importantly, these results were confirmed when brain tissue from organ donors with Alzheimer’s dementia was analyzed. However, when the mice were genetically engineered to prevent the production of Medin, there was far less amyloid beta deposits and consequently less damage to the blood vessels.
“Worldwide there are only a handful of research groups working with the medina,” says Neher. Recently, a US study reported that Medina levels may be elevated in Alzheimer’s patients. However, it was not clear whether this increase is only a consequence of the disease or is one of the causes.
“We have now been able to show through many experiments that Medina actually promotes vascular pathology in Alzheimer’s models,” says Neher. Thus, medina deposits are effectively a cause of damage to blood vessels. “And this suggests that the medina is one of the causes of the disease,” concludes Neher.
In their studies, the researchers stained tissue sections from both mice and Alzheimer’s patients to visualize specific proteins. They were thus able to show that Medin and amyloid-beta are deposited together in the blood vessels of the brain – the technical term for this is co-localization. In a next step, they were able to show that these two amyloids also accumulate, i.e. form mixed deposits. “Surprisingly, Medin directly interacts with amyloid-beta and promotes its aggregation, which was completely unknown,” summarizes Neher.
It is precisely from this idea that the researchers draw hope to develop a new therapy. “Medin could be a therapeutic target to prevent vascular damage and cognitive impairment resulting from the accumulation of amyloid in the blood vessels of the brain,” they conclude. In expert circles it is undisputed that, in addition to beta-amyloid aggregates in the brain tissue, vascular disorders, i.e. reduced functionality or damage to vessels, also promote the development of Alzheimer’s disease. Therefore, treatments that target not only the plaques but also the affected blood vessels could help patients.
In a next step, it must be clarified whether the Medina aggregates can be removed therapeutically and whether this intervention really affects cognitive performance. The scientists first want to test it in mouse models because these reflect the pathological changes in Alzheimer’s patients “very well”.