Liver protein can cause Alzheimer’s disease in the brain

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Amyloid protein made in the liver can cause neurodegeneration in the brain, according to a new study published in the open access journal PLOS Biology, by John Mamo of Curtin University in Bentley, Australia, and colleagues. Because protein is believed to be a key factor in the development of Alzheimer’s disease (AD), the results suggest that the liver may play an important role in the onset or progression of the disease.

Amyloid-beta (A-beta) deposits in the brain are one of the pathological features of AD and are involved in neurodegeneration in both human patients and animal models of the disease. But A-beta is also present in peripheral organs, and blood levels of A-beta correlate with cerebral amyloid load and cognitive impairment, increasing the chance that peripherally produced a-beta may contribute to the disease. Testing this hypothesis has been difficult, as the brain also produces A-beta and distinguishing protein from the two sources is a challenge.

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

The findings from this study indicate that peripheral-derived A-beta has the ability to cause neurodegeneration and suggest that liver-produced A-beta may potentially contribute to human disease. If this contribution is significant, the findings may have important implications for understanding Alzheimer’s disease. To date, most disease models have focused on brain overproduction of A-beta, which mimics the rare genetic cases of human Alzheimer’s. But for the vast majority of MA cases, overproduction of A-beta in the brain is not thought to be central to the etiology of the disease. In contrast, lifestyle factors may play a more important role, including a high-fat diet, which could accelerate hepatic A-beta production.

The effects of peripheral A-beta on brain capillaries may be critical in the disease process, Mamo adds. “Although additional studies are now needed, this finding shows that the abundance of these toxic protein deposits in the blood could be addressed through a person’s diet and some drugs that could specifically target the amyloid. lipoprotein, reducing its risk or slowing the progression of Alzheimer’s disease. ”