Alzheimer’s researchers make the case that infections as common as gingivitis could be the disease’s root cause. 

Beta-amyloid plaques—sticky globs of protein—build up in the brains of people with Alzheimer’s disease. For decades, scientists have focused on developing new treatments like recently approved Leqembi and work-in-progress donanemab to help the brain clear these plaques and slow Alzheimer’s progression. 

But what if the plaques aren’t the root cause of Alzheimer’s

Alzheimer’s expert Ruth Itzhaki at the University of Manchester, and many other researchers, believe that infectious diseases are responsible for kickstarting Alzheimer’s disease. There’s a shortlist of menacing microbes that scientists think could trigger the disease, most notably the Herpes virus and bacteria responsible for gingivitis. Viruses like COVID-19, which seems to have long-term effects on the brain, are drawing scrutiny, too. 

How infections could trigger Alzheimer’s

Many people infected with viruses or bacteria don’t develop symptoms. But that doesn’t mean these imposters aren’t making their way through the body—and into the brain. In some cases, microbes like Herpes can “sleep” inside of brain cells for decades. After their initial infection, people become asymptomatic carriers. 

“Events such as stress, infection, or immunosuppression reactivate it [the microbes] causing damage to the brain,” Itzhaki told Being Patient. In response, the brain activates its immune system to fight the pathogen, releasing beta-amyloid proteins which also have antimicrobial properties

According to researchers who ascribe to the infectious hypothesis of Alzheimer’s, beta-amyloid plaques accumulate only as a response to other infections. 

Herpes and Alzheimer’s

A 2018 study by researchers in Taiwan looked at data from thousands of electronic health records. They found that people diagnosed with a Herpes infection were more than 2.5 times more likely to develop Alzheimer’s or other forms of dementia 10 years later. 

Another study published in 2020 found that carriers of Herpes who took antiviral drugs had a lower risk of developing Alzheimer’s than those who did not take the antivirals.

These are just two of the many studies researchers point to when making the case that Herpes might cause, or at least, activate, Alzheimer’s. And their argument is prompting new drug trials. For example, a new clinical trial called VALAD is underway to test whether an antiviral medication, valacyclovir, can halt the progression of mild Alzheimer’s in patients who are Herpes carriers. 

Gingivitis and Alzheimer’s

A 26-year-long study published in 2020 found that the gingivitis-causing bacteria Porphyromonas gingivalis increased Alzheimer’s risk. Coupled with evidence from animal models which found P. gingivalis caused inflammation and brain damage, researchers started testing drugs that kill this bacteria. 

Cortexyme tested the antibiotic atuzaginstat to see if it could slow the rate of cognitive decline in mild or moderate Alzheimer’s disease. Their clinical trial included 643 participants but ultimately found no differences in cognitive decline between the people who received a placebo and those that received the drug. 

The company is now testing a new drug that might stop some of the damaging proteins produced by this bacteria — called gingipains — that may be causing inflammation in Alzheimer’s.

The success of these clinical trials would mean a deeper understanding of what causes Alzheimer’s and make more disease-modifying treatments available. Since these drugs don’t require an intravenous infusion, they might also be more affordable for patients.

Other viruses and bacteria?

Herpes and gingivitis aren’t the only two potential culprits being studied for their close links to Alzheimer’s disease. Many researchers believe that the bacteria and viruses living in the gut might be involved in cognitive decline or Alzheimer’s. Scientists have recently found that the presence or absence of certain bacteria in the gut could predict Alzheimer’s disease well in advance of any symptoms. Other scientists believe that the bacteria that causes Lyme disease or COVID could also contribute to dementia. 

Together these findings suggest that the immune system, which responds to bacteria and viruses, may also play a key role in Alzheimer’s. But more research is needed to understand whether these microbial organisms on their own can cause the disease.