Could it be that Alzheimer's disease stems from the toxic remnants of the brain's attempt to fight off infection?
Provocative new research by a team of investigators at Harvard leads to this startling hypothesis, which could explain the origins of plaque, the mysterious hard little balls that pockmark the brains of people with Alzheimer's.
The Harvard researchers report a scenario seemingly out of science fiction. A virus, fungus or bacterium gets into the brain, passing through a membrane — the blood-brain barrier — that becomes leaky as people age. The brain's defense system rushes in to stop the invader by making a sticky cage out of proteins, called beta amyloid. The microbe becomes trapped in the cage and dies. What is left behind is the cage — a plaque that is the unique hallmark of Alzheimer's.
So far, the group has confirmed this hypothesis in neurons growing in petri dishes as well as in yeast, roundworms, fruit flies and mice. There is much more work to be done to determine if a similar sequence happens in humans, but plans — and funding — are in place to start those studies.
The work began when Robert D. Moir, of Harvard Medical School and Massachusetts General Hospital, had an idea about the function of amyloid proteins, normal brain proteins whose role had long been a mystery.
Moir noticed that they looked a lot like proteins of the innate immune system, a primitive system that is the body's first line of defense against infections.
He began collaborating with Rudolph E. Tanzi in a study funded by the National Institutes of Health and the Cure Alzheimer's Fund. The idea was to see if amyloid trapped microbes in living animals and if mice without amyloid proteins were quickly ravaged by infections that amyloid could have stopped.
The answers, they reported, were yes and yes.
In one study, the group injected Salmonella bacteria into the brains of young mice that did not have plaques.
"Overnight, the bacteria seeded plaques," Tanzi said. "The hippocampus was full of plaques, and each plaque had a single bacterium at its center."