Nature reports a previously completely unknown new target for Alzheimer's treatment

This protein, along with amyloid β, is deposited in
the blood vessels of the brain of Alzheimer's patients.
Researchers at DZNE discovered this so-called co-aggregation phenomenon
.
They have now published their observations in the prestigious journal Nature
.
Medin was known more than 20 years ago, but its impact on the disease was previously underestimated
.
We were able to demonstrate that medin significantly enhances pathological changes in blood vessels in Alzheimer's patients," said Dr.
Jonas Neher, who led the study
.
The Hertie Institute for Clinical Brain Research in Tübingen, the University of Tübingen and several international institutions and partners are also involved in this long-term project
.

Medin belongs to the starch group
.
Of these proteins, amyloid β is best known because it clumps together
in the brains of Alzheimer's patients.
These aggregates are deposited directly in brain tissue as plaques and also in blood vessels, damaging nerve cells and blood vessels
, respectively.
But while much of the research has focused on amyloid β, medin is not the focus of
interest.
Neher explains: "There is little pathological evidence, that is, clinically significant findings associated with medin, which is often a prerequisite
for more in-depth research on amyloid.
"

In fact, however, medin is found in the blood vessels of almost all people over the age of 50, making it the most common known amyloid protein
.
The team initially found that medin develops even in aging mice, and reported the discovery
two years ago in the scientific journal PNAS.
Studies at the time found that the older the mice, the more medin accumulated in the blood vessels of the brain
.
What's more, when the brain becomes active and triggers an increase in blood supply, blood vessels with medin precipitation expand more slowly
than those without medin precipitation.
However, the ability of blood vessels to dilate is essential
for providing the brain with optimal oxygen and nutrition.

In the latest findings, the researchers specifically studied Alzheimer's
on this basis.
First, they were able to show in a mouse model of Alzheimer's that if amyloid-β were also present, the accumulation of medin in the blood vessels of the brain would be stronger
.
Importantly, these findings were confirmed
when brain tissue from organ donors with Alzheimer's was analyzed.
However, when mice were genetically modified to prevent the formation of medin, amyloid β deposition was significantly reduced and therefore less damage to blood vessels
.

Jonas Neher said: "There are only a few research groups in the world working on medin
.
" Recently, a study in the United States reported that medin levels may be elevated
in people with Alzheimer's disease.
However, it is not clear whether this increase is simply a consequence of the disease or one of
its causes.
"We have now been able to demonstrate through many experiments that medin actually promotes vascular pathology in Alzheimer's models," Neher said
.
Therefore, medin deposition is indeed a cause
of vascular damage.
"This suggests that medin is one of the causes of this disease," Neher said
.

In their study, the researchers stained tissue sections from mice and Alzheimer's patients to make specific proteins visible
.
This allowed them to show that medin and amyloid proteins β co-deposited in the blood vessels of the brain — colocalization is the jargon
for this.
Next, they were able to show that the two amyloids also co-aggregate—that is, form mixed deposits
.
"Surprisingly, medin interacts directly with amyloid β and promotes its aggregation – something completely unknown," Jonas Neher summarizes the findings
.

It is from this insight that researchers offer hope
for the development of a new treatment.
They concluded: "Medin can be used as a therapeutic target to prevent vascular damage and cognitive decline
due to amyloid buildup in cerebral blood vessels.
" Experts are undisputed that in addition to the aggregation of amyloid β in brain tissue, vascular alterations also contribute to the development of Alzheimer's disease, that is, reduced or damaged
blood vessel function.
Therefore, treatment not only for plaque, but also for the affected blood vessels can help the patient
.

As a next step, it is necessary to determine whether medin aggregates can be removed from treatment and whether this intervention really has an effect
on cognitive performance.
The scientists first wanted to test it on mouse models because these models well reflect pathological changes
in Alzheimer's patients.

Medin co-aggregates with vascular amyloid-β in Alzheimer’s disease