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Alzheimer's, liver protein to blame? The results of an innovative study

The "blood-brain" pathway that intoxicates the latter, producing Alzheimer's degeneration, could originate from the liver.

Gianluca Ricciodi Gianluca Riccio
in Medicine
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Liver

Several studies now suggest that peripheral beta-amyloid (Aß) metabolism is associated with the risk of Alzheimer's. Mice engineered to synthesize human β only in the liver exhibited concomitant neurodegeneration with capillary dysfunction and neurovascular inflammation. Photo: National Institute on Aging / National Institutes of Health.

19 September 2021
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According to a new study in mice published online in the journal PLoS Biology, a probable cause of the Alzheimer's disease is the release from the blood into the brain of particles carrying fat and toxic liver proteins.

"We have identified the probable 'blood-brain pathway' that can lead to Alzheimer's, the most prevalent form of dementia globally," says study senior author Professor John Mamo, director of the Curtin Health Innovation Research Institute at Curtin University.

We knew that the defining feature of people living with Alzheimer's disease was the progressive build-up of toxic protein deposits within the brain called beta-amyloid. What we didn't know is where the amyloid came from, or why it was deposited in the brain. We now know that these toxic protein deposits are carried into the brain by liver-produced particles called lipoproteins.

John Mamo
Lipoproteins, liver and alzheimers
A "close-up" lipoprotein

Managing the liver, managing Alzheimer's?

“This blood-brain pathway that originates from the liver is significant,” says the scientist. "Because if we can manage blood levels of lipoprotein-amyloid and prevent them from leaking into the brain, this opens up potential new treatments to prevent Alzheimer's and slow memory loss."

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Building on previous research showing that beta-amyloid is produced outside the brain with lipoproteins, Professor Mamo and his colleagues tested the blood-brain pathway using genetic engineering of mouse models. Mice with liver "engineered" to produce human lipoproteins.

The results

“It's as we expected,” Mamo says. The study found that the mouse models that produce lipoprotein-amyloid in the liver suffered from brain inflammation. Not only that: they accelerated brain cell death and memory loss, ”said Professor Mamo.

Further studies are needed, and tests also on human subjects. An important opening opens up, however. This finding shows that the abundance of these toxic protein deposits in the blood could potentially be addressed through a person's diet.

Some drugs may specifically target lipoprotein amyloid, thereby reducing their risk or slowing the progression of Alzheimer's disease.

tags: alzheimer
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