A new study linking Alzheimer’s and infection may turn the scientific and medical community’s understanding and treatment of the disease upside down. The study, published in Science Translational Medicine this past week, suggests that current therapies may be targeting the wrong culprit when it comes to treating the degenerative brain disorder.
Neurologists Rudolph Tanzi and Robert Moir headed the team of researchers from Harvard Medical School and Massachusetts General Hospital. Their study found that a protein that has previously been found to play an integral role in the development of Alzheimer’s disease also acts to protect the brain from infection.
The processes involved in Alzheimer’s disease are complex. The protein, which goes by the name amyloid beta, is generally believed among the researchers who specialized in Alzheimer’s disease to be the root cause of the degenerative condition. Amyloid beta is a waste product, and as such, it was not believed to play any useful role in bodily functions.
As it accumulates in the brain, it builds up into the sticky plaque that damages nerve cells at the synapse, or where they communicate with each other. The declining memory and cognitive functions that are typically associated with Alzheimer’s disease are the result.
Most current drug therapies for Alzheimer’s disease target amyloid beta, with a view to clearing the brain of the protein, but the new study suggests that may not be the best approach.
The Alzheimer’s – infection connection
The idea for the study on Alzheimer’s and infection goes back about six years, when Moir found similarities between amyloid beta and another protein called LL37, which plays a crucial role in protecting the brain against infections. The amino acid signature found in human beta amyloid is also found in most mammals, including coelacanth fish that are 400 million-years-old. Moir explains in an article in Scientific American.
“These types of proteins, although small, are very sophisticated in what they do. And they’re very ancient, going back to the dawn of multicellular life.”
In addition to their beneficial properties, antimicrobial proteins like LL37 and amyloid beta can also produce harmful effects when their functioning goes out of control. Because of the similarities, the researchers set out to find whether amyloid beta also had an antimicrobial function in the brain.
The team performed a number of experiments on human and mouse cells, then on mice and roundworms. A clear relationship emerged between the presence of amyloid beta and protection against infection.
What they found most surprising was that when Salmonella bacterium was injected into the brains of “Alzheimer’s model mice” – or mice who have been genetically altered to mimic symptoms of the disease by over-producing amyloid beta – the plaques of amyloid beta protein began to form almost immediately, each surrounding a cell of the Salmonella infection. Tanzi is quoted in Scientific American.
“We didn’t know this was even possible, that amyloid plaques would form rapidly overnight.”
The new study suggests that Alzheimer’s could be caused by an infection that results in an overproduction of amyloid beta. It appears as if the introduction of the infectious bacteria causes the amyloid beta to go into overdrive in an attempt to encapsulate it and protect the brain by preventing it from adhering to brain cells in a reaction gone awry. A buildup of amyloid beta as a result of infection causes a chain reaction that leads to inflammation and eventually to full-blown Alzheimer’s disease.
As the brain and body age, the immune system grows weaker, which may make it easier for such infections to arise in the brain. Untreated infections that remain or recur in the brain may change the role of amyloid beta from protective to destructive.
Alzheimer’s, infection and treatment options
Current treatments for Alzheimer’s focus on ridding the brain of amyloid beta entirely and reducing inflammation via the immune system. The new study suggests that targeting the innate immunity pathways (the body’s first line of defense against infection) or the infecting microbes directly may be a more effective approach.
Many in the scientific community remain skeptical of the premise, however. As quoted in Science Magazine, Colin Masters, a neuroscientist at the University of Melbourne in Australia, called the results “very contrived in the sense that they don’t bear a direct relationship to what we see in the human condition.”
Moir and his team remain convinced of the direction they will continue to pursue. The next step will be systematically testing the brains of deceased Alzheimer’s patients for the pathogens that cause infection.
“We’re at the top of a mountain with a freshly formed layer of snow. Where you go is where you choose. There’s so much to explore.”
The news about Alzheimer’s and infections gives hope to the millions of people worldwide who face this tragic disease.
[Image via Juan Gaertner/Shutterstock]