Thought-provoking new research by a team of investigators at Harvard University raises the question of whether Alzheimer’s disease stems from the toxic remnants of the brain’s attempt to fight off infection.
This startling hypothesis could explain the origins of plaque, the mysterious hard little balls that pockmark the brains of people with Alzheimer’s. It is still early, but Alzheimer’s experts not associated with the work are captivated by the idea that infections, including ones that are too mild to elicit symptoms, may produce a fierce reaction that leaves debris in the brain, causing Alzheimer’s.
The idea makes sense, and the Harvard group’s data, published last Wednesday in the journal Science Translational Medicine, supports it. If it holds up, the hypothesis has major implications for preventing and treating this degenerative brain disease.
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, 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 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 needed to determine if a similar sequence happens in humans, but plans–and funding–are in place to start those studies, involving a multicenter project that will examine human brains.
“It’s interesting and provocative,” said Dr. Michael W. Weiner, a radiology professor at the University of California, San Francisco, and a principal investigator of the Alzheimer’s Disease Neuroimaging Initiative, a large national effort to track the progression of the disease and look for biomarkers like blood proteins and brain imaging to signal the disease’s presence.
Dr. David Holtzman, a professor and the chairman of neurology at the Washington University School of Medicine in St. Louis, was also intrigued. “It is obviously outside the box,” he said. “It really is an innovative and novel study.”
At this point, the Harvard researchers have what many say is an intriguing hypothesis, but they readily acknowledge that much work lies ahead. The Cure Alzheimer’s Fund is starting a large collaborative project that will use gene sequencing technology to carefully look for microbes in brains from people who had Alzheimer’s and those who did not.
Researchers will also look for microbes in plaques found in human brains. That, though, “is a big, big second step,” Dr. Tanzi said. “First we need to ask whether there are microbes that may sneak into the brain as we age and trigger amyloid deposition. Then we can aim at stopping them.” (Source: The New York Times)
Monday, May 30, 2016 / Vol. 24 / No. 21