Subvert mainstream theories! JAD: The reduction of specific proteins causes Alzheimer's disease, not the accumulation of amyloid plaques!

It is easy to talk about Alzheimer's disease, because this degenerative neuropathy tends to occur in elderly patients over 65 years old, and because the cause is not clear, there is no targeted drug
that can effectively cure it.

The direction of drug development requires the investigation of the cause of the disease, and it is in this area that it is currently hindered
.
In particular, the groundbreaking paper of the mainstream theory of the cause of Alzheimer's disease, "β amyloid theory", was questioned, and it suddenly became a lingering haze
.

Where is Alzheimer's research headed?

News on October 4, a research team led by Alberto Espay, MD, and Andrea Sturchio, MD, from the University of Cincinnati (UC), in collaboration with the Karolinska Institute (KI) in Sweden, was published in the Journal of Alzheimer's Disease A new study in the Journal of Alzheimer's Disease supports the hypothesis that Alzheimer's disease is caused by a drop in the level of a specific protein, not the accumulation of amyloid plaques!

Note that the emphasis here is on the reduction of protein, is the reduction! This is in contrast to the popular theory of the "β amyloid theory" that has recently been questioned.

Mainstream theories have been frequently questioned not once or twice, and a paper published in Nature on June 2 this year has long confirmed that Alzheimer's disease is not caused by amyloid β, which subverts our traditional impression that Alzheimer's disease "has extracellular amyloid plaque formation first, followed by nerve cell death", the paper proposes First nerve cells die, followed by extracellular amyloid plaques"
.

Think about it this way, even if the amyloid plaque outside the cell is removed, the victim cell has long died, what is the use of the drug developed in this way? The direction is not right!

Let's take a look at this blockbuster study
on October 4.

The study still focused on a protein
called β-amyloid.
This protein normally performs functions in the brain in a soluble form, meaning it is soluble in the cellular matrix, but sometimes it hardens into lumps called amyloid
plaques.

For more than 100 years, the conventional wisdom in the field of Alzheimer's research has been that Alzheimer's disease is caused
by the accumulation of amyloid plaques in the brain.
But Espay and his colleagues' research supports another theory: plaques are simply the result of declining levels of soluble β-amyloid in the
brain.
These decreased levels of soluble β-amyloid because normal proteins are transformed into abnormal amyloid plaques in the event of biological disturbances, metabolic abnormalities, or infection stress.

Espay, professor of neurology at the University of Cincinnati School of Medicine, director and chair professor of the Center for Families with Parkinson's Disease and Movement Disorders at the Gardner Institute for Neuroscience at the University of Cincinnati, and physician in the health system at the University of Cincinnati, explains: "Paradoxically, as we age, many of us build plaque in our brains, but very few develop dementia
.
”

How can this be explained?

The researchers note that over the years, many studies and clinical trials have aimed at reducing amyloid plaques in the brain, and some have reduced plaques, but none have slowed the progression of
Alzheimer's disease.

What's more, in some clinical trials that reduced soluble β-amyloid levels, patients experienced deterioration in clinical outcomes
.

This suggests that reduced levels of soluble β amyloid in the brain may be the cause of
Alzheimer's disease.

To confirm their hypothesis, the research team analyzed β-amyloid levels in a group of patients with mutations (APP, PSEN1, or PSEN2) that predict overexpression of amyloid plaques in the brain, which is thought to make them more likely to develop Alzheimer's disease
.

However, people who have accumulated plaque in their brains who produce high levels of soluble β-amyloid have a lower risk of developing dementia over a
three-year period.

Ultimately, the research team confirmed that when the baseline level of soluble β-amyloid in the brain is above 270 pg per milliliter (1 picogram equals one trillionth of a gram), people can maintain cognitive normalcy
regardless of the number of amyloid plaques in the brain.

In fact, as early as June 28 last year, another blockbuster study published by the research team in the Lancet sub-issue has found that regardless of the accumulation of plaques in the brain, people with high levels of soluble β-amyloid have normal cognitive ability, while people with low levels of soluble β-amyloid are more likely to have cognitive impairment
.

This new research is even more solid for his new theory!

After the new study was released, Espay cautioned fellow scholars: "If you can jump out of the prejudices we have formed for a long time and not be influenced by our predecessors, then you will find that the neurodegenerative process is caused by the soluble β-amyloid protein that we lose, not by the amyloid plaque of what we acquire!" ”

However, scientists are too easily influenced by authority, and have been stubbornly hitting the south wall, obviously the road is not passable, but they have been hitting the wall
.

The research doesn't stop and continues to move forward, with teams investigating whether increasing levels of soluble β-amyloid in the brain is a beneficial treatment
for Alzheimer's patients.

Espay notes that it's important to make sure that elevated levels of protein introduced into the brain don't turn into amyloid plaques, as a soluble version of this protein is needed for normal function to have an impact
in the brain.

Within the broader spectrum of brain diseases, the researchers say they believe similar hypotheses that cause neurodegeneration can be applied to other diseases, including Parkinson's disease and Creutzfeldt-Jakob disease (CJD), where research continues
.

In Parkinson's disease, for example, a normal soluble protein in the brain called α-synuclein (α-synuclein) hardens into a deposit called a lewy body
.
The researchers hypothesize that Parkinson's disease is not caused by Lewy body aggregation in the brain, but by a decrease in normal soluble α-synuclein levels
.

The research direction of degenerative diseases of the brain has been clear, and the author hopes that this is a sunshine road to the truth!

References: https://medicalxpress.
com/news/2022-10-decreased-proteins-amyloid-plaques-tied.
html.