The idea could be a break-through that leads to new treatments.
Scientists have known for some time that infections can increase the risk of Alzheimer’s disease. Now, for the first time, a team has found signs of higher-than-normal levels of Gram-negative bacteria associated with disease in the brains of people who develop Alzheimer’s late in life.
The team, at the University of California, Davis, examined 18 brains posthumously, and in all of them found greater numbers of E. coli in blood vessels and amyloid plaques, the tell-tale tiny hard balls we see in the brains of dementia patients. This doesn’t mean that E. coli or another bacteria is a cause of the mental decline, but it’s possible.
The same lab found a link between this kind of bacteria and the production of the plaques in animals.
“Finding bacterial molecules in the brain was a surprise, and finding more in the Alzheimer’s brains was a great surprise,” said Frank Sharp, MD, professor of neurology and senior author on the paper. If the bacteria actually played a role in aggravating Alzheimer’s, “we could immunize against [it] or treat Gram-negative infections more vigorously than we normally do,” Sharp said.
The bacteria may be a byproduct of other processes. It’s also possible that once people have Alzheimer’s more of the bacteria gets into the brain.
But a separate group of researchers, at Harvard, has a provocative theory about how infections might lead to Alzheimer’s. The plaque may be like trash on a battle-ground, generated by the body’s fight against the infection.
Here’s how it might work, in more detail: The brain is protected by a membrane, called the blood-brain barrier, that becomes leaky as we age. If a virus, fungus, or bacterium gets through, we respond by building a kind of cage to trap the invader. The amyloid plaques may be the cage.
Amyloid proteins are common in the brain, but we haven’t known their function. It may be that they are part of the immune response. The infections may even be too mild for the patient to notice them, which explains why the connection isn’t obvious.
Top researchers in the field see the idea as promising. “It’s interesting and provocative,” said Michael W. Weiner, MD, a radiology professor at the University of California, San Francisco, and a principal investigator of the Alzheimer’s Disease Neuroimaging Initiative, a large national project looking for early signs of the disease.
The amyloid-cage theory would fit the fact that a number of kinds of bacteria, and also viruses, have been associated with Alzheimer’s. In a 2015 overview of the research on infection and Alzheimer’s, a separate team concluded that the risk of Alzheimer’s increased from four to 10 times in people with detectable spirochetal infection. Spirochetes are a kind of bacteria, often found in mud, sewage, and polluted water, which cause some of the most tragic human illnesses, including syphilis. This research also found that infection with the respiratory bacteria “Cpn” increased the likelihood of Alzheimer’s by a factor of five.
Another study compared how Alzheimer’s affects the body over time to the path of dementia caused by syphilis. The researchers concluded that the two illnesses were similar enough to conclude that Alzheimer’s might be “prevented” by seeking out and treating spirochete and other infections.
The Harvard group, led by Robert D. Moir, MD, of Harvard Medical School and Massachusetts General Hospital, has worked with animals to establish the idea that amyloid proteins are part of the immune response.
They’ve seen the cages sprout overnight in mice brains. The team injected salmonella bacteria into plaque-free brains of young mice that had did not have plaques. The next day, those mice brains were full of amyloid plaques, each with a single bacterium in the middle. Mice that didn’t have the capacity to make beta amyloid didn’t make plaques and died more quickly from the infection.
The amyloid cages appeared in the hippocampus of the first group of mice. That’s important, because the hippocampus is the site of learning and memory, where the amyloid plaques characteristic of Alzheimer’s appear in humans, and also the leakiest part of the blood-brain barrier.
Why would some people get Alzheimer’s younger, before the membrane deteriorates? We know that in people with the gene ApoE4, the brain is less able to sweep out amyloid once it forms.
Other people may overproduce the substance, so it clumps even in the absence of an infection.
People who get infections but don’t develop dementia may have a better ability to sweep out the plaque or a sturdier blood-brain membrane.
If the theory proves correct, it may lead to answers to the treatment puzzle: we might treat infections more aggressively or differently, or interfere with the chain of events at other points.
February 13, 2017
Janet O’Dell, RN