Amyloid-beta Produced in the Liver May Play Role in Alzheimer’s
Amyloid-beta produced in peripheral organs, specifically the liver, may be implicated in the brain neurodegeneration observed in Alzheimer’s disease, according to a mouse study.
The study, “Synthesis of human amyloid restricted to liver results in an Alzheimer disease–like neurodegenerative phenotype,” was published in PLOS Biology.
Deposits of amyloid-beta in the brain are a hallmark of Alzheimer’s. However, given that both the brain and liver produce amyloid-beta, it has been challenging for scientists to determine the source of amyloid-beta found in the brain of Alzheimer’s patients or animal models of the disease.
In humans, peripheral amyloid-beta from the liver travels through the bloodstream as part of a complex with triglyceride-rich lipoproteins (TRLs), basically a way to transport fat-soluble particles through the bloodstream. Previous studies have shown that diets rich in saturated fats increase the amount of TRLs available and increase inflammation in the brain.
In this study, researchers genetically engineered mice to produce human amyloid-beta only in their livers, this way allowing them to detect whether the liver or the brain was the potential cause for the neurodegeneration.
These animals had significantly higher amounts of circulating amyloid-beta in their blood (roughly 30% more than healthy controls) and this circulating form of human amyloid-beta was complexed with TRLs, just as it does in humans.
Additionally, there was significantly more inflammation in the brains of mice that produced human amyloid-beta versus healthy control mice. Genetically engineered mice showed significantly more neurodegeneration — approximately two-fold higher — as compared to healthy control mice, at 18 months (equivalent to roughly 63 human years).
These mice also showed increased inflammation in the blood vessels of the brain, in addition to increased dysfunction in those same blood vessels, all of which is commonly seen in Alzheimer’s.
Mice with increased circulating levels of amyloid-beta were also more likely not to perform as well in learning tests where they were required to form new memories.
This study seems to show that peripherally-derived amyloid-beta, specifically from the liver, contributes toward the neurodegeneration and neuroinflammation seen in Alzheimer’s disease.
“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,” John Mamo, PhD, of Curtin University in Bentley, Australia, said in a press release.
Understanding the peripheral metabolism of amyloid-beta protein can help scientists better determine the risk for Alzheimer’s disease.
“Lifestyle and particularly dietary interventions for prevention, or reconsideration of lipid-modulating drugs,” may be included when considering potential Alzheimer’s risk-reduction strategies, according to the researchers.