A protein in the brain believed to be a key contributor to the development of Alzheimer’s is also produced in the liver, according to new research that says the football-sized organ may play a larger role in the progression of the disease than previously thought.
Alzheimer’s disease is a degenerative condition that is believed to be the result, in part, of the accumulation of amyloid in the brain that leads to the slow death of neurons. This process eventually produces symptoms of memory loss, difficulty thinking or problem solving and changes in mood and behaviour.
The buildup of amyloid, also known as A-beta, in the brain is thought to be one of the key causes of the neurodegeneration that gives rise to Alzheimer’s, the most common cause of dementia in the world. But the protein is also produced in peripheral organs, raising the possibility that A-beta created elsewhere in the body can travel to the brain and contribute to the disease. This hypothesis has been difficult to test, however, because the brain also produces the protein and distinguishing between the two sources has been difficult.
The current study, published in the journal PLOS Biology, sought to rectify this by developing a mouse model that was only capable of producing A-beta in its liver cells. The experiments revealed that the protein was able to make its way to the brain by travelling through the blood on triglyceride-rich lipoproteins — the same path it takes in humans. Once there, the mice began to experience brain atrophy and neurodegeneration, in addition to neurovascular inflammation and dysfunction of cerebral capillaries, all common hallmarks of Alzheimer’s disease. These mice became unable to perform learning tests that depend upon the function of the brain’s hippocampus, a structure vital to the creation of new memories.
The results reveal that peripherally produced A-beta can lead to neurodegeneration and that the proteins created in the liver potentially play a role in the development of Alzheimer’s disease in humans. The findings may have major implications, particularly if that contribution is found to be significant. Most current models of Alzheimer’s disease are rooted in the overproduction of A-beta in the brain, a process that mirrors what is seen in rare genetic cases of the disease. But in the majority of cases of the disease, A-beta overproduction is not believed to be central to disease development.
The current findings suggest lifestyle factors, such as a high-fat diet, might be accelerating the production of A-beta in the liver, which, in turn, can affect the progression of Alzheimer’s. The work opens new avenues for exploration and potential therapies to treat the 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,” said John Mamo, one of the authors of the study from Curtin University in Bentley, Australia.
There are currently over 500,000 Canadians living with dementia, with another 25,000 diagnosed with the progressive disease every year, according to the Alzheimer Society. Two-thirds of those diagnosed over the age of 65 are women. With the rate at which the disease is growing, it costs over $12-billion a year to care for patients.
Dave Yasvinski is a writer with Healthing.ca