Can Infections Cause Alzheimer’s Disease?

Scientists have found high levels of bacterial infections in the brains of people with Alzheimer’s disease. Is there a link between infections and Alzheimer's?

Scientists have known for some time that infections can increase the risk of Alzheimer’s disease. There may also be 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. 

Gram-negative bacteria are more resistant to antibiotics, protected by a strong cell wall. They include E. coli, Helicobacter pylori, and salmonella. 

Researchers at the University of California, Davis examined 18 brains posthumously. All had greater numbers of E. coli in blood vessels and amyloid plaques, the tell-tale tiny hard balls seen in the brains of dementia patients. That doesn’t mean that E. coli or other bacteria cause mental decline, but it’s possible. 

The same lab found a link between the bacteria and the production of the plaques in animals.

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“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 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 disease. The plaque may be like trash on a battleground, generated by the body’s fight against the infection. 

Here’s how it might work. A membrane, called the blood-brain barrier, protects the brain. It becomes leaky as you age. If a virus, fungus, or bacterium gets through, the brain builds a kind of cage to trap the invader. The amyloid plaques may be the cage. 

Amyloid proteins are common in the brain, but no one knows their function. They may be 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.

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The amyloid-cage theory would fit the fact that several kinds of bacteria, and also viruses, have been associated with Alzheimer’s. In one 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, that cause some of the most tragic human illnesses, including syphilis. The 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 when a syphilis infection causes dementia. The researchers concluded that the two illnesses were similar enough to conclude that finding and treating spirochete and other infections might prevent Alzheimer’s. 

Separate research documented a link between Alzheimer’s and herpes-like viruses. People with Alzheimer’s show higher-than-normal levels of antibodies to herpes, a sign of a previous infection.

The Harvard group, led by Robert D. Moir, MD, of Harvard Medical School and Massachusetts General Hospital, (now deceased) worked with animals to establish the idea that amyloid proteins are part of the immune response. 

The researchers saw the amyloid cages sprout overnight in mice brains. The team injected salmonella bacteria into plaque-free brains of young mice that 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. It is also the leakiest part of the blood-brain barrier. 

Why would some people get Alzheimer’s younger, before the membrane deteriorates? Researchers 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, causing clumps even in the absence of an infection. 

People who get infections but don’t develop dementia may have a sturdier blood-brain membrane or a better ability to sweep out the plaque. 

If the theory proves correct, it may lead to answers to the treatment puzzle: Aggressive or different treatment of infections may interfere with the chain of events. 

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