Alzheimer’s disease (AD) and other forms of dementia are associated with a build-up of toxic proteins in the brain, and new research indicates that these harmful compounds may in fact originate in the liver. According to the study authors, this finding could open up new pathways for the treatment of certain neurodegenerative conditions, with lifestyle factors such as diet playing a potentially key role in staving off cognitive decline.
Appearing in the journal PLoS Biology, the study attempted to solve a long-standing riddle concerning the origin of amyloid proteins, which accumulate as plaques in the brain and destroy neurons. While these proteins are produced within the brain itself, they are also created in other organs and transported through the bloodstream as lipoproteins.
This has led to some degree of uncertainty as to which organ produces the amyloid proteins that cause AD. To investigate, the researchers used mice that had been genetically engineered to produce amyloid proteins only in the liver.
Using a number of imaging techniques, the researchers observed how these proteins were transported in the blood by triglyceride-rich lipoproteins, just as they are in humans. They were also able to detect the movement of these compounds into the brain, where they accumulated and triggered a cascade of harmful effects.
“Our research shows that these toxic protein deposits that form in the brains of people living with Alzheimer’s disease most likely leak into the brain from fat carrying particles in blood, called lipoproteins,” explained study author Professor John Mamo in a statement.
In addition to displaying an abundance of cerebral amyloid plaques, the mice also suffered from “chronically exaggerated rates of neurodegeneration.” This entailed the death of neurons within key brain regions associated with cognitive function, as well as neurovascular inflammation and dysfunction of cerebral capillaries – all of which are seen as hallmarks of Alzheimer’s in humans.
Predictably, these mice then performed poorly on cognitive tests that rely on the formation of new memories in the hippocampus. For instance, they displayed an impaired ability to remember which areas of their enclosure generated an electric shock, and were, therefore, less likely to avoid these spaces than regular mice.
Taken together, these results point towards the possibility that AD may be caused by liver proteins leaking into the brain from the bloodstream.
Summing up the significance of this research, Mamo explained that “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.”