A groundbreaking study from Curtin University, Australia, reveals that the liver-produced amyloid protein can induce neurodegeneration in the brain.
This discovery implies a potential significant role for the liver in Alzheimer’s disease (AD) progression or onset. The study was published in the open-access journal PLOS Biology and led by John Mamo.
Deposits of amyloid-beta (A-beta) in the brain are one of the key pathological hallmarks of AD, implicated in neurodegeneration in both humans and animal models.
A-beta is also found in peripheral organs, and blood levels of the protein correlate with cerebral amyloid burden and cognitive decline.
This suggests that peripherally produced A-beta may contribute to AD. However, since the brain also produces A-beta, distinguishing protein from the two sources has been a challenge.
Study Design and Findings
The researchers overcame this difficulty by creating a mouse model that produces human A-beta exclusively in liver cells.
They demonstrated that this protein was carried in the blood by triglyceride-rich lipoproteins, similar to humans, and moved from the periphery into the brain.
The researchers found that these mice developed neurodegeneration and brain atrophy, accompanied by neurovascular inflammation and cerebral capillaries dysfunction, symptoms commonly observed in AD.
The affected mice performed poorly on a learning test that depends on hippocampal function, a brain structure critical for new memory formation.
Implications
The study suggests that A-beta produced in the liver could potentially contribute to human disease. If so, this finding could have significant implications for understanding Alzheimer’s disease.
Previous models of AD primarily focused on the brain’s overproduction of A-beta, similar to rare genetic cases of human Alzheimer’s. However, for most AD cases, brain overproduction of A-beta is not considered central to the disease’s etiology.
Instead, lifestyle factors like a high-fat diet, which might boost liver production of A-beta, could play a crucial role.
Mamo proposes that the impact of peripheral A-beta on brain capillaries may be critical in the disease process.
Further research is needed, but these findings suggest that toxic protein deposits in the blood could potentially be managed through diet or drugs that target lipoprotein amyloid, thereby reducing Alzheimer’s risk or slowing disease progression.
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The study was published in PLoS Biol.
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