Nature: Significant progress! In Alzheimer's disease, the protein medin interacts with β amyloid and is co-deposited in blood vessels in the brain

The protein medin is deposited with β amyloid (Aβ) in the blood vessels of the brain of Alzheimer's patients
.
In a new study, researchers from research institutions such as the German Research Center for Neurodegenerative Diseases and the University of Tübingen discovered this so-called co-aggregation
.
The findings were published online on November 16, 2022 in the journal Nature under the title "Medin co-aggregates with vascular amyloid-β in Alzheimer's disease
.
"

Dr Jonas Neher, corresponding author of the paper and from the German Research Centre for Neurodegenerative Diseases, said: "Medin has been known for more than 20 years, but its impact on the disease has previously been underestimated
.
We were able to find that pathological changes in the blood vessels of Alzheimer's patients were significantly enhanced
by medin.
”

The protein medin belongs to amyloid
.
Of these proteins, Aβ is the most famous because it clumps
in the brains of people with Alzheimer's disease.
These aggregates are then deposited both directly in the brain tissue as so-called plaques and in its blood vessels, damaging nerve cells and blood vessels
, respectively.
But while much of the research has focused on Aβ, medin has not been in the spotlight
.

Neher explains, "There is little pathological evidence --- clinically compelling findings associated with medin, which is often a prerequisite
for more in-depth research on one amyloid protein.
" ”

However, medin is actually found in the blood vessels of almost all people over the age of 50, making it the most common known amyloid protein
.
Neher and his team initially found that medin produces even in aging mice, and reported the findings two years ago in the journal PNAS (PNAS, 2020, doi:10.
1073/PNAS.
2011133117).

The older the mice, the more medin accumulated in the blood vessels of the brain, which was discovered
at the time.
What's more, when the brain becomes active and triggers an increase in blood supply, blood vessels with medin deposits expand more slowly
than those without medin.
However, the ability of blood vessels to dilate is important
for optimally supplying oxygen and nutrients to the brain.

The protein medin interacts directly with β amyloid, promoting its aggregation
.
Image from Nature, 2022, doi:10.
1038/s41586-022-05440-3
.

For their latest results, the authors built on this foundation and specifically studied Alzheimer's disease
.
First, they were able to show in a mouse model of Alzheimer's disease that medin accumulates more
strongly in blood vessels in the brain if Aβ deposits are also present.
Importantly, these findings were confirmed
when the brain tissue of organ donors with Alzheimer's disease was analyzed.

However, when mice were genetically modified to stop medin formation, the Aβ deposits that appeared were significantly reduced and, as a result, less
damage to blood vessels.

Neher said, "There are only a handful of research groups in the world working on medin
.
"Recently, a study in the United States reported that medin levels may be increased
in people with Alzheimer's disease.
However, it remains unclear whether this increase is simply a consequence of the disease or whether it is one of the
causes.

Neher said, "We are now able to find through many experiments that medin actually promotes vascular lesions
in Alzheimer's disease models.
So medin deposits are indeed a cause
of vascular damage.
This suggests that medin is one of the causes of
this disease.
”

In their study, the authors stained tissue sections from mice and Alzheimer's patients to make specific proteins visible
.
This allowed them to confirm that medin and Aβ are deposited together in the blood vessels of the brain--- colocalization is the technical term
for this.
In a next step, they were able to show that the two amyloid proteins also co-aggregate, i.
e.
form mixed deposits
.

Neher said, "Surprisingly, medin interacts directly with Aβ and promotes its aggregation – something completely unknown
.
”

It is from this new insight that these authors see hope
in developing a new treatment.
They concluded, "Medin may be a therapeutic target to prevent vascular damage and cognitive decline
due to amyloid accumulation in blood vessels in the brain.
" ”

Experts are uncontroversial that in addition to the aggregation of Aβ in brain tissue, vascular alterations--- that is, decreased or damaged blood vessel function--- also contribute to the development of
Alzheimer's disease.
Therefore, therapies that target not only plaque but also affected blood vessels may help Alzheimer's patients
.

In the next step, it is now necessary to determine whether medin aggregates can be removed with a therapeutic approach and whether this intervention really has an impact
on cognitive performance.
The authors first hope to test in mouse models because these models well reflect pathological changes
in Alzheimer's patients.
(Biovalley Bioon.
com)

Resources:

Jessica Wagner et al.
 Medin co-aggregates with vascular amyloid-β in Alzheimer's disease, Nature, 2022, doi:10.
1038/s41586-022-05440-3.