The protein medin, like the protein amyloid-, accumulates in the blood vessels of Alzheimer’s patients’ brains. DZNE researchers discovered this ‘co-aggregation.’ Their discovery has subsequently been published in the prestigious journal 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 “explains Dr Jonas Neher, the study’s principal investigator and director of the DZNE’s Tubingen location.
The University of Tubingen, the Hertie Institute for Clinical Brain Research in Tubingen, and a variety of international organisations and cooperation partners all contributed to this extensive study. Amyloid is exemplified by Medin. The most well-known of these proteins is amyloid-, which clumps in the brains of Alzheimer’s patients. The brain’s blood arteries and tissue are both injured as a result of these aggregates’ eventual deposition as plaques, which in turn destroy the brain’s nerve cells and blood vessels.
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, on the other hand, is the most common amyloid and may be found in the blood vessels of nearly everyone over the age of 50. Jonas Neher and his colleagues discovered that medin appears in old mice and published their findings in the scientific journal PNAS two years ago.
It was revealed at the time that medin accumulated more in the mice’s brain blood vessels as they matured.
Furthermore, as the brain becomes active and blood flow increases, medin-deposited blood vessels expand more slowly than medin-free blood vessels. However, the capacity of blood vessels to develop is critical for providing the brain with adequate oxygen and nutrients.
On top of that, the researchers’ most recent studies focused on Alzheimer’s disease. First, scientists were able to show in Alzheimer’s mouse models that the presence of amyloid deposits leads medin to accumulate substantially more strongly in the blood arteries of the brain.
Importantly, the study of brain tissue from organ donors with Alzheimer’s disease validated these findings. However, far fewer amyloid- deposits accumulated in mice whose genes were changed to prevent the production of medin, resulting in fewer blood vessel damage.
“There are only a handful of research groups worldwide working on medin at all,” says Jonas Neher. A recent study from the United States found that medin levels may rise in Alzheimer’s sufferers. However, it was unclear if this rise was simply a result of the sickness or if it was one of the reasons.
“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.
The scientists employed tissue pieces from mice and Alzheimer’s patients that had been coloured so that certain proteins could be detected in their study. They were able to show that medin and amyloid- are co-localized, or deposited together, in the blood vessels of the brain. They were able to show that these two amyloids co-aggregate, or form mixed deposits, in a later stage.
According to Jonas Neher, the findings “amazingly, medin interacts directly with amyloid- and enhances its aggregation – which was entirely unknown.” This realisation has given the researchers hope for the development of a revolutionary therapy.
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.”
Alzheimer’s disease is undoubtedly facilitated by vascular alterations, impaired function, or damage to blood vessels, as well as amyloid-aggregates in brain tissue. Patients may benefit from medicines that target both damaged blood vessels and plaques.
The next phase will be to see if medin aggregates can be eliminated therapeutically and, if so, whether this intervention ha any effect on cognitive performance. The researchers intend to test this in mice initially since animal models properly replicate the pathogenic changes in Alzheimer’s sufferers.
