PNAS: Down syndrome, like Alzheimer's, is a biprion disease

People with Down syndrome develop neurodegenerative tangles and plaques associated with Alzheimer's in their brains and often show signs of
neurodegenerative diseases at the age of forty and fifty.
A new study by researchers at the University of California, San Francisco suggests that these tangles and plaques are caused by β amyloid (?) and tau prion-driven, they found that this was the same
cause of Alzheimer's disease in 2019.

Prions start as normal proteins, then deform and multiply
themselves.
They spread through tissues like infections by forcing normal proteins to adopt the same misfolded shape
.
In Alzheimer's and Down syndrome, with the use of Alzheimer's and Down syndrome? and tau prions accumulate in the brain, they cause neurological dysfunction, often manifested as dementia
.

According to the National Institute on Aging, most people with Down syndrome develop Tau protein tangles and Tau protein tangles before the age of 40.
Protein plaques, at least 50% of which develop Alzheimer's
as people age.

The new study, published November 7, 2022 in the Proceedings of the National Academy of Sciences, highlights how a better understanding of Down syndrome can also lead to new insights
into Alzheimer's disease.

"There are two diseases here — Down syndrome and Alzheimer's — that have completely different etiologies, but we're seeing the same disease biology
.
It's really surprising," said Stanley Prusiner, MD, senior author of the study who won the Nobel Prize
in 1997 for discovering prions.

In the United States, Down syndrome is the most common neurodegenerative disease in young people, while Alzheimer's disease is the most common
in adults.

Down syndrome occurs because chromosome 21 has an extra copy
.
Among the many genes on this chromosome is a gene called APP, which codes
for a major component of β amyloid.
With extra copies of the gene, people with Down syndrome produce too many apps, which may explain why they form amyloid plaques
early in life.

A younger brain provides clearer images

We already know that both Down syndrome and Alzheimer's are present? Plaques and tau protein tangles
.
Previously, researchers had shown that these neurodegenerative traits were caused by prions in Alzheimer's, and they wondered if the same abnormal protein
was present in the brains of people with Down syndrome.

Prusina, director of the UCSF Institute for Neurodegenerative Diseases, part of the Weill Institute for Neuroscience, said that while extensive research has been done on these plaques and entanglements in the brains of Alzheimer's patients, discerning which changes in the brain come from aging and which are caused by prion activity, can be a challenge
.

"Because we see the same plaque and tangled pathology in people with Down syndrome, studying their brains can give us a better understanding of the early processes of disease formation, before
the brain is complicated by all the changes that occur during aging," he said.
"Ideally, you want to treat these early stages
.
"

In the Alzheimer's study, the team took a different approach than the new method they used in Alzheimer's research, looking at donated tissue samples
from deceased people with Down syndrome obtained from biobanks around the world.
From 28 samples of donors aged 19 to 65, the researchers were able to isolate measurable quantities from almost all of them.
and tau prions
.

New insights can lead to prevention

The results of the study not only confirmed that prions are associated with neurodegeneration in Down syndrome, but also confirmed that prions are associated with neurodegeneration in Down syndrome.
Driving the formation of tau protein tangles and amyloid plaques, a relationship that has long been suspected but has not been proven
.

"The field has long tried to understand what the intersection between these two pathologies is," said Dr.
Carlo Condeiro, the study's lead author and a member of
the UCSF Institute for Neurodegenerative Diseases.
The case of Down syndrome confirms this view; Now you have this extra chromosome to drive?, and there is no tau gene
on the chromosome.
Therefore , it is indeed by increasing the expression of Ał to initiate the production
of tau protein.
”

Condello said that by studying the brains of people with Down syndrome, this insight and other information gathered will give us a better understanding of
how prions begin to form in the first place.

Whether brain tissue from Down syndrome will prove to be the ultimate model for treating Alzheimer's remains to be seen
, the researchers said.
While the two diseases share many similarities in prion pathobiology, there are some differences that may create limitations
.

Still, the researchers say studying plaques and tangles in Down syndrome is a promising way to identify specific prions
that appear at the earliest stages of the disease process.
This discovery opens up new prospects not only for treating Alzheimer's disease, but perhaps even for preventing Alzheimer's disease
.

"If we can understand how this neurodegeneration begins, we're one big step closer to being able to intervene at a meaningful point and really stop the formation of these big
brain lesions," Condello said.