A Harvard study supports the theory, and may pave the way for new research.
Researchers have long believed that the devastating protein plaques that collect in the brains of people with Alzheimer's disease have no useful function, and their presence does nothing but obliterate once vital memories and minds.
A study published this week in the journal Science Translational Medicine suggests that the plaques—made of a protein called amyloid beta—may actually have a role after all, possibly in fighting off infection, and that Alzheimer's may be an unwelcome result of this legitimate purpose.
This could change the thinking about a disease that has not seen a new drug approval since 2003 and stubbornly eluded scientists' efforts not only to treat it, but even to understand it.
Any practical applications of the new research, however, are still a long way off.
"It's intriguing, it's exciting, and it opens new opportunities for intervening in the disease, but at the same time it's very preliminary and speculative," says Ronald Petersen, MD, PhD, director of the Mayo Clinic Alzheimer's Disease Research Center in Rochester, Minnesota. "I wouldn't go too far in saying that this is the answer or breakthrough."
But it is different.
"The [theory] that has guided therapeutic strategies for more than 30 years is that amyloid beta is a freak, that what it does is abnormal and has no function," says study corresponding author Robert Moir, PhD, of the Genetics and Aging Research Unit at the MassGeneral Institute for Neurodegenerative Disease in Boston.
Five years ago, Moir and colleagues demonstrated that amyloid beta could kill pathogens, among them Candida yeast, in test tubes.
The criticism of that study was expected: Test tubes aren't humans.
So the researchers took the idea a step further, not quite to humans but at least to living organisms, including mice, round worms, and fruit flies.
In this study, creatures that had been genetically engineered to produce high levels of amyloid beta were able to fight off infections from Salmonella and other microorganisms quickly and successfully. Those with low levels couldn't fight them off nearly as well.
"The really surprising thing was it doesn't just kill microbes like an antibiotic," explains Moir, who is also assistant professor of neurology at Harvard Medical School.
Instead, the plaques use the exact same structure that is the hallmark of Alzheimer's—steel-strength fibrils aggregating into plaques—to entomb the offenders.
The plaques did this quickly and they didn't let go, becoming permanent residents, as jailers of microbes serving several life sentences.
"The good side is the bugs don't get out, but it's very hard for us to clear the amyloid," says Moir.
The study authors hypothesize that more bugs manage to cross the blood-brain barrier as we age, triggering the whole system into overdrive.
In other words, very low-level chronic infection and the inflammation and immune response that go with it may be culprits in Alzheimer's.
If this turns out to be true (and proving it is a long way off), then drugs targeting this portion of the immune system may pay off, as might a strategy of lessening the plaques rather than eliminating them entirely.
"It opens up doors," says Moir. "It doesn't invalidate all the stuff that's been done but it puts it in a new perspective."
"It's not going to be a simple answer," adds Dr. Petersen. "It's going to take a combination of approaches but this might be a component."