Alzheimer’s disease: Medin as a new target

Scientists have discovered that the role of the Medin protein in Alzheimer’s disease has been underestimated until now. It can be a new target for attacks.

Medin protein is also deposited along with amyloid-β protein in the blood vessels of the brain of Alzheimer’s patients. Scientists from the German Center for Neurodegenerative Diseases (DZNE) discovered this so-called coaggregation. They now publish their observations in Nature.

“Although Medin has been known for around 20 years, its effect on diseases has been underestimated until now. We were able to demonstrate that Medin significantly increases the pathological changes in the blood vessels of patients with Alzheimer’s disease,” says the leader of the study, Dr. Jonas Neher from the DZNE location in Tübingen. The Hertie Institute for Clinical Brain Research in Tübingen, the University of Tübingen and other international institutions and cooperation partners were also involved in the study.

Medin is not the center of interest yet

Medin belongs to the group of amyloids. Of these proteins, amyloid-β is the best known because it accumulates 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, causing damage to nerve cells and blood vessels. Therefore, while many studies have looked at amyloid-β, Medin has not been a focus until now. “There was little evidence of pathology, that is, of a clinically striking finding in connection with Medin – and this is often a prerequisite for a more detailed study of amyloid,” explains Jonas Neher.

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However, medin is actually 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 Medin even develops in aging mice and reported it in the journal two years ago PNAS about this discovery. The older they get, the more Medina accumulates in the blood vessels of the mice’s brains – that was the finding at the time. And when the brain becomes active and requires more blood supply, vessels with Medina deposits dilate more slowly than those without Medina. However, this ability to expand is important for the optimal supply of oxygen and nutrients to the brain.

Significantly less amyloid-β deposits without Medina

For their latest results, the researchers built on this foundation and focused specifically on Alzheimer’s disease. In mouse models of Alzheimer’s disease, they were able to demonstrate that Medin accumulates even more in the blood vessels of the brain if amyloid-β deposits are also present there. Corresponding findings could then be demonstrated in the brain tissue of organ donors with Alzheimer’s dementia. However, if the mice were genetically modified so that Medin could not form, there were significantly fewer amyloid-β deposits and, as a result, significantly less damage to blood vessels.

“There are only a handful of working groups in the whole world that work on the Medina at all,” says Jonas Neher. A previous study from the US recently described that the level of medicine in Alzheimer’s patients is increasing. However, it remains unclear whether this is only a consequence of the disease or whether it is one of the causes. “We have now been able to demonstrate in multiple experiments that Medin promotes vascular pathology in models of Alzheimer’s disease,” says Neher. Thus, Medina deposits are actually the cause of blood vessel damage. “And that’s a sign that it’s one of the causes of the disease,” says Neher.

In their studies, the researchers stained tissue sections from both mice and patients with Alzheimer’s disease in such a way that specific proteins were visible. This allowed them to show that Medin and amyloid-β deposit together in the blood vessels of the brain – co-localization is the technical term for this. Through further experiments, they were able to demonstrate in the next step that these two amyloids also aggregate together – that is, they form mixed accumulations. “It is amazing that Medin directly interacts with amyloid-β and promotes its aggregation – this was still completely unknown,” summarizes the results of Jonas Neher.

A new therapeutic target?

It is from this that scientists draw hope for the development of a possible treatment. “Medin could be a therapeutic target to prevent vascular damage and cognitive decline due to amyloid accumulation in brain blood vessels,” they conclude. In professional circles, it is indisputable that the cause of Alzheimer’s disease is not only amyloid-β aggregates in the brain tissue, but also vascular changes – that is, reduced function or damage to blood vessels. So if you treat not only the plaques, but also the affected blood vessels, it could help the patient.

In the next step, it is now necessary to clarify whether already formed Medina aggregates can be therapeutically removed and whether this intervention really has an effect on memory performance. The researchers want to test this first in mouse models, as these reflect the pathological changes in Alzheimer’s patients very well.

This text is based on a Press Release of the German Center for Neurodegenerative Diseases (DZNE). We have an original publication for you here and referenced in the text.

Image source: Mauro Gigli, splash

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