Science

Landmark study presents evidence Alzheimer’s disease begins in the liver

Landmark study presents eviden...
Using a newly developed preclinical model, new research demonstrates how toxic amyloid proteins are produced in the liver and then travel to the brain
Using a newly developed preclinical model, new research demonstrates how toxic amyloid proteins are produced in the liver and then travel to the brain
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Using a newly developed preclinical model, new research demonstrates how toxic amyloid proteins are produced in the liver and then travel to the brain
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Using a newly developed preclinical model, new research demonstrates how toxic amyloid proteins are produced in the liver and then travel to the brain

An impressive new study is presenting robust evidence showing the toxic proteins thought to be the cause of Alzheimer’s disease may be produced in the liver and travel through the blood before landing in the brain causing neuron damage.

For several decades it has been generally accepted that Alzheimer’s disease is caused by the accumulation of amyloid proteins in the brain. These proteins form toxic aggregations known as plaques and it is these plaques that damage the brain.

Although doubts are growing regarding the veracity of the “amyloid hypothesis,” the build up of these plaques is still the most prominent physiological sign of Alzheimer’s. And one of the more interesting hypotheses going around suggests these damaging amyloid proteins originate in the liver.

The big challenge in investigating this liver-amyloid hypothesis is that amyloid is also produced in the brain. Most mouse models used in Alzheimer’s research involve engineering the animals to overexpress amyloid production in the central nervous system, which only really resembles the minority of humans suffering from hereditary early-onset Alzheimer’s. The vast majority of people developing the disease instead experience what is known as sporadic Alzheimer’s, where the disease develops in older age, with no familial or genetic history.

The breakthrough in this new research is the development of a new animal model of Alzheimer’s disease. Here, the researchers engineered a mouse to produce human amyloid proteins solely in the liver, and this allowed for novel observations into how these proteins can enter the bloodstream and travel to the brain.

John Mamo, lead researcher on the project from Curtin University in Australia, says this new study offers clear evidence of a “blood-to-brain pathway.” Using the newly developed mouse model the study shows how amyloid produced in the liver can move to the brain and cause damage leading to pathological signs similar to those seen with Alzheimer’s disease.

“As we predicted, the study found that mouse models producing lipoprotein-amyloid in the liver suffered inflammation in the brain, accelerated brain cell death and memory loss,” says Mamo. “This ‘blood-to-brain pathway’ is significant because if we can manage the levels in blood of lipoprotein-amyloid and prevent their leakage into the brain, this opens up potential new treatments to prevent Alzheimer’s disease and slow memory loss.”

Mamo is already moving ahead with a human clinical trial based on this liver-amyloid hypothesis. Prior studies have shown a pre-existing drug used to manage high cholesterol, known as probucol, can suppress production of amyloid in the liver.

The clinical trial began this year and plans to recruit around 300 subjects with mild Alzheimer’s-related dementia. The primary outcome will be to investigate whether daily doses of probucol for two years leads to a clinically significant slowing of cognitive decline.

But if this liver-amyloid hypothesis is further validated in future studies a number of other outcomes could arise. Alzheimer’s disease risk may be estimated at a young age by evaluating an individual’s propensity for synthesizing amyloid in the liver. Plus, dietary interventions could hypothetically be deployed to improve liver health and decrease a person’s risk of developing Alzheimer’s.

“While further studies are now needed, this finding shows the abundance of these toxic protein deposits in the blood could potentially be addressed through a person’s diet and some drugs that could specifically target lipoprotein amyloid, therefore reducing their risk or slowing the progression of Alzheimer’s disease,” says Mamo.

The new research was published in the journal PLOS Biology.

Source: Curtin University

3 comments
3 comments
vincem
Thanks for highlighting research on this topic.
Atri Wilson
Great that modern science finally caught up! The Chinese Meridian Charts from 5 000 yrs ago, already depicted frontal lobe disorders such as Alzheimer's, epilepsy, depression etc. as a liver problem.
Gomer
Oh, great... Now they've determined that the amyloid may be coming from the liver... How about researching the problem causing the body to produce it instead. I'm sure this will lead to another class of worthless drugs like statins that reduce LDL instead of addressing what's causing the high production.