Deposits of amyloid beta protein (A-beta) in the brain are known to be one of the pathological features of Alzheimer’s disease and are implicated 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 brain amyloid load and cognitive decline , increasing the possibility that peripherally produced A-beta may contribute to the disease. . Testing that hypothesis has been difficult, as the brain also produces A-beta, and distinguishing the protein from the two sources is quite an experimental challenge.
A work published in the journal PLOS ONE suggests that the liver, through the production of this protein, may play an important role in the onset or progression of the disease. The researchers developed an animal model with a mouse that only produced A-beta in liver cells and showed that the protein was transported in the blood by triglyceride-rich lipoproteins, as in humans , and passed from the periphery to the brain. . The mice developed neurodegeneration and brain atrophy, which was accompanied by neurovascular inflammation and brain capillary dysfunction, both commonly associated with Alzheimer’s disease. Affected mice performed poorly on a learning test that depends on the function of the hippocampus , the structure of the brain that is essential for the formation of new memories.
The findings of this study indicate that peripherally derived A-beta has the ability to cause neurodegeneration and suggest that A-beta produced in the liver is a potential contributor to disease. If that contribution is significant, the findings may have important implications for understanding Alzheimer’s disease. To date, most models of the disease have focused on brain overproduction of A-beta, which mimics the rare genetic cases of Alzheimer’s disease in humans. But for the vast majority of cases, overproduction of A-beta in the brain is not believed to be central to the etiology of the disease. Instead, lifestyle factors may play a bigger role, including a high-fat diet, which could speed up A-beta production in the liver.
Limitations to work
“This study in small groups of mice is interesting, but there is a long way to go to understand if liver proteins could contribute to human Alzheimer’s disease,” reflects Tara Spiers-Jones, deputy director of the Center for the Discovery of the Brain Sciences from the University of Edinburgh in statements to Science Media Center . “This article provides data showing that in mice, the expression of an Alzheimer’s-related gene in the liver causes brain changes. While these findings are interesting, it should be remembered that the mice do not show the typical brain changes associated with Alzheimer’s disease, and neither was a full characterization of brain cell death done.
Referencia: Lam et al ‘Synthesis of human amyloid restricted to liver results in an Alzheimer disease–like neurodegenerative phenotype’ PLOS Biology
