Peripherally Produced Amyloids Could Cause Neurodegeneration

An amyloid protein made in the liver can cause neurodegeneration in the brain, according to a new study published in PLOS Biology, by researchers at the University of Bentley, in Australia.

In the current study, the authors developed a mouse that produces human a-beta only in liver cells. They showed that the protein was carried in the blood by triglyceride-rich lipoproteins, just as it is in humans, and passed from the periphery into the brain. They found that mice developed neurodegeneration and brain atrophy, which was accompanied by neurovascular inflammation and dysfunction of cerebral capillaries, both commonly observed with Alzheimer’s disease. Affected mice performed poorly on a learning test that depends on the function of the hippocampus, the brain structure that is essential for the formation of new memories.

The findings from this study indicate that peripherally derived A-beta has the ability to cause neurodegeneration and suggest that A-beta made in the liver is a potential contributor to human disease. To date, most models of the disease have focused on brain overproduction of A-beta, which mimics the rare genetic cases of human Alzheimer’s. But for the vast majority of AD cases, overproduction of A-beta in the brain is not thought to be central to the disease etiology. Instead, lifestyle factors may play a more important role, including a high-fat diet, which might accelerate liver production of A-beta.

The effects of peripheral A-beta on brain capillaries may be critical in the disease process, lead researcher John Mamo adds. “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.”