Startling new research by a team from Harvard poses an interesting proposition: Alzheimer’s disease could come from the toxic remains of the brain’s efforts to fight off infection, reports the New York Times.
Alzheimer’s experts who have not been involved in the study have been interested in the idea that infections, even the mild asymptomatic ones, may produce a huge reaction that leaves remnants in the brain, causing Alzheimer’s. This could explain the origins of the hard little balls of plaque present in the brains of people with Alzheimer’s – something that has long been a mystery.
This idea, while certainly revolutionary, makes sense, according to the Harvard groups’ research, which was published in the journal Science Translational Medicine. If the hypothesis holds up to scrutiny, the implications for preventing and treating this degenerative disease are incredible.
According to the Harvard research, a virus, fungus or bacterium that gets into the brain passes through the blood-brain barrier, a membrane that becomes leaky as people age. The brain’s defenses rush in to stop this invasion by making a sticky cage out of proteins called beta amyloids. The virus or whatever is invading, becomes trapped in this cage and dies. What is left behind is the cage, which forms the plaque that identifies Alzheimer’s.
The group was able to confirm this hypothesis by using neurons growing in petri dishes, as well as in yeast, flies, roundworms and mice. There is plenty of work and research to be done to further these same tests in humans, but plans and funding are currently in the works, focusing on a multicenter project that will examine human brains.
Scientists and doctors are intrigued at the study and its results, and have lauded its efforts. “It’s interesting and provocative,” said Dr. Michael W. Weiner, a radiology professor at the University of California, San Francisco, and principal investigator of the Alzheimer’s Disease Neuroimaging Initiative.
The study began when Dr. Robert Moir, of the Harvard Medical School and Massachusetts General Hospital, had an idea regarding the function of amyloid proteins, which are normal brain proteins that have puzzled scientists as to what role they played.
The proteins were originally thought to be just waste matter that accumulated in the brain with age, but Moir noticed that they looked similar to proteins in the immune system. In other parts of the body, the same proteins trap harmful microbes and white blood cells come to clean everything up. Moir thought the amyloids might be a part of this process.
Moir collaborated with Dr. Rudolph Tanzi, also from the Harvard Medical School and Massachusetts General Hospital, in a study funded by the National Institutes of Health and the Cure Alzheimer’s Fund. The goal was to see if amyloid proteins trapped microbes in living animals and if mice that did not have amyloid proteins were more likely to be infected by diseases that amyloids could have prevented.
Following the experiments conducted, Moir and Tanzi had their answers: affirmative. For years, scientists have looked at the plaque in Alzheimer’s patients’ brains as some sort of trash, but few ever bothered to look into other explanations.
Dr. Samuel Gandy, a neurology and psychiatry professor at the Icahn School of Medicine at Mount Sinai Hospital in New York, says that there has been a long and convincing body of research that explains how Alzheimer’s happens. There were a few clues that something else was going on, but they did not make sense.
Weiner points out an example: there were reports that Alzheimer’s patients had higher levels of antibodies to herpes compared to people who did not have the disease. “The suggestion that herpes was causative seemed a bit far-fetched,” Weiner said.
This new study, Gandy and Weiner say, provides what could be the better explanation. Another research conducted by Dr. Berislav Zlokovic, the director of the Zilkha Neurogenetic Institute at the University of Southern California, focusing on the blood-brain barrier also fits well with this new hypothesis.
Of course, this is still all hypothetical and there is more to Alzheimer’s than just the immune system, and plenty of questions to be answered regarding the disease, such as why people who have a mutated gene develop Alzheimer’s at an early age, and why not everyone who has had a brain infection develops this degenerative disease.
The Harvard researchers have a long way to go. The Cure Alzheimer’s Fund is taking a “big, second step,” according to Tanzi, by starting a large-scale project that will use gene sequencing technology to look for microbes in Alzheimer’s patients’ brains and those who don’t have the disease. Researchers will also look for microbes in plaques in human brains.