Could it be that Alzheimer’s disease stems from the toxic remnants of the brain’s attempt to fight of 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 study, published in the journal Science Translational Medicine, posits that infections, including ones that are too mild to elicits symptoms, may produce a fierce reaction that leaves debris in the brain, causing Alzheimer’s. If it holds up, the hypothesis has major implications for preventing and treating AD.

The Harvard researchers reported the following scenario. 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 my making a sticky cage out of proteins, called beta amyloid. The microbe, like a fly in a spider web, becomes trapped in the cage and dies. What is left behind is the cage, a plaque that is the pathological hallmark of AD.

So far, the researchers have confirmed their hypothesis in neurons growing in petri dishes, as well as in yeast, roundworms, fruit flies, and mice. Work remains to be done to determine if humans might experience a similar outcome; the funding for a stage 1 clinical trial is in place to commence the study shortly.

The amyloid proteins have traditionally been thought of as garbage that accumulates in the brain with age. But researchers have begun to take note of the similarities between amyloid and the proteins of the innate immune system, a primitive system that is the body’s first line of defense against infections.

In a study funded by the National Institutes of Health and the Cure Alzheimer’s Fund, Dr. Robert D. Moir and Dr. Rudolph E. Tanzi, of Harvard Medical School and Massachusetts General Hospital sought to determine if amyloid trapped microbes in living animals 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 researchers injected salmonella bacteria into the brains of young mice that did not have plaques. “Overnight, the bacteria seeded plaques,” Dr. Tanzi said. “The hippocampus was full of plaques and each plaque had a sing bacterium at its center. In contrast, mice that did not make beta amyloid succumbed more quickly to the bacterial infection and did not make plaques.

Of course, there must be more to Alzheimer’s than the brain’s innate immune system. What about people that have a mutated gene that guarantees they will develop the disease at an early age?

For them, Dr. Tanzi said, the problem is that they vastly overproduce beta amyloid. There is so much that it clumps on its own, without the presence of microbes.

Not everyone who has had a brain infection develops Alzheimer’s, though. Why are some more vulnerable than others? According to this new theory, it probably has to do with the brain’s ability to clear out the balls of beta amyloid after they have killed microbes.

At this point, the Harvard researchers have what many say is an intriguing hypothesis, but they acknowledge that much work lies ahead.