Study reveals a new approach for Alzheimer's therapies

BERLIN: The protein medin builds up in the blood vessels of Alzheimer's patients' brains together with the protein amyloid. Researchers from the DZNE team discovered this co-aggregation. Their discovery has since been made public in the esteemed magazine Nature.

"Although Medin has been around for more than 20 years, its impact on illnesses was previously underrated. We were able to demonstrate that medin considerably increases the pathological changes in the blood vessels of Alzheimer's patients" explained Dr Jonas Neher, the study's principal investigator and director of the DZNE's Tubingen location.

This lengthy research also included participation from the University of Tubingen, the Hertie Institute for Clinical Brain Research in Tubingen, and a number of foreign organisations and cooperation partners. Medin is an example of amyloid.

The most well-known of these proteins is amyloid-, which aggregates in Alzheimer's patient's brains. The brain's blood arteries and tissue are both damaged as a result of these aggregates' subsequent deposition as so-called plaques, which inflict damage on the brain's nerve cells and blood vessels, respectively.

But while amyloid- has been the subject of numerous investigations, medin has not drawn much attention. Jonas Neher notes that "there was minimal evidence of pathology, that is, of a clinically noteworthy finding connected with medin," and that "pathology is frequently the prerequisite for a more in-depth research of an amyloid."

Medin, however, is the most prevalent amyloid known and is present in the blood arteries of practically everyone over the age of 50. Jonas Neher discovered with his colleagues that medin even manifests in ageing mice, and he published this finding in the scientific journal PNAS two years ago.At the time, it was discovered that medin accumulated more in the mice's brain blood arteries as they aged.

Additionally, medin-deposited blood vessels expand more slowly than medin-free blood vessels when the brain gets active and causes a rise in blood flow. However, the ability of blood vessels to grow is crucial for providing the brain with oxygen and nutrients at its best.

On top of this foundation, the researchers focused on Alzheimer's illness for their most recent findings. First, they were able to demonstrate in Alzheimer's mice models that the presence of amyloid- deposits causes medin to collect significantly more strongly in the brain's blood vessels.

Importantly, these conclusions were supported by the analysis of brain tissue from organ donors who had Alzheimer's disease. However, much fewer amyloid- deposits formed in mice that had their genes altered to inhibit the development of medin, and as a result, fewer blood vessel injuries happened.

"There are only a handful of research groups worldwide working on medin at all," says Jonas Neher. Most recently, a study from the U.S. reported that medin levels may increase in Alzheimer's patients. However, it remained unclear whether this increase is merely a consequence of the disease or whether it is one of the causes.

"We have now been able to show through many experiments that medin actually promotes vascular pathology in Alzheimer's models," Neher said. So medin deposits are indeed a cause of blood vessel damage. "And this indicates that medin is one of the causes of the disease," Neher said.

In their investigation, the scientists used tissue sections from mice and Alzheimer's patients that had been dyed so that particular proteins could be seen. They were able to demonstrate that medin and amyloid- are co-localized, or deposited together, in the brain's blood arteries.

They were able to demonstrate that these two amyloids also co-aggregate, that is, create mixed deposits, in a subsequent stage. The findings, according to Jonas Neher, "amazingly, medin interacts directly with amyloid- and increases its aggregation - this was completely unknown."

The researchers have hope for the creation of a novel treatment because of this realisation. As a result of amyloid buildup in the brain's blood vessels, they suggest that Medin "may be a therapeutic target to avoid vascular injury and cognitive decline."

The development of Alzheimer's disease is unquestionably aided by vascular changes, diminished function or damage to blood vessels, in addition to amyloid-aggregates in brain tissue. Therefore, therapies that target both damaged blood arteries and plaques may benefit patients.

The next step will be to investigate whether medin aggregates can be removed therapeutically, and if so, whether this intervention has any real impact on cognitive function. Since mouse models accurately represent the pathological changes in Alzheimer's patients, the researchers first plan to test this in mice.