Common Pneumonia Bacteria in the Eye Linked to Alzheimer’s

Once considered controversial, the idea that microbes like viruses and bacteria may contribute to Alzheimer’s disease is gaining traction. 

Recent observational studies suggest that the shingles vaccine could reduce dementia risk, while respiratory infections like COVID-19 and the flu may accelerate the disease.  

In earlier studies, some researchers had found evidence of Chlamydia pneumoniae — a common cause of pneumonia and sinus-infections — in the brain of those with Alzheimer’s. Others, however, failed to detect it, throwing the earlier findings into doubt. 

A recent study from researchers at Cedars-Sinai, published in Nature Communications, used multiple detection techniques to help settle the case. In autopsied brain and retina samples from people with Alzheimer’s they confirmed the presence of C. pneumoniae, and for the first time, showed it lingers in the retina as well. 

Maya Koronyo-Hamaoui, PhD, a professor at Cedars-Sinai Health Sciences University and senior author of the study, told Being Patient, “Higher retinal and brain burden” of C. pneumoniae “is associated with more severe Alzheimer’s disease-related pathology and worse cognition.” 

She added that their experiments in animal and cell models “support an infection-associated” mechanism that might accelerate Alzheimer’s in some individuals. 

Eyeing a potential driver of Alzheimer’s

In this study, Koronyo-Hamaoui’s team analyzed post-mortem retina and brain tissue from 104 people — 51 who died with Alzheimer’s, 16 with mild cognitive impairment (MCI) caused by Alzheimer’s, and 37 healthy controls.

“Our data show that a portion of individuals with normal cognition are positive to C. Pneumoniae,” Koronyo-Hamaoui said. “This is a common respiratory bacteria that most people at a certain age will be exposed to.“ 

The researchers used the average levels of the bacteria in healthy controls as a baseline. About 38 to 40 percent of people who were cognitively healthy carried elevated levels of the bacteria in their brain or retina, compared to 60 to 79 percent of those with MCI and 100 percent of those with Alzheimer’s. 

Higher bacteria levels in the retina correlated with lower cognitive test scores and more beta-amyloid plaques, a key hallmark of Alzheimer’s. Carriers of the Alzheimer’s risk gene ApoE4 also had higher levels of bacteria in the retina, regardless of cognitive status. Measuring C. pneumoniae levels in the retina was also effective in distinguishing between cognitively healthy and Alzheimer’s individuals, though it failed to separate healthy controls from MCI. 

Through further analysis and experiments in animal and cell models, the team showed that C. pneumoniae activated a protein complex called the NLRP3 inflammasome, potentially driving inflammation, an increase in beta-amyloid plaques, and cognitive impairment. 

Does the study prove that eye bacteria causes Alzheimer’s?

Koronyo-Hamaoui’s study adds to growing evidence that infections may play a role in Alzheimer’s, though it does not provide proof of causation.

“While the findings are provocative, the study demonstrates association rather than definitive causation in humans,” Dr. Sharon Fekrat, an eye surgeon and professor of neurology and ophthalmology at Duke University, who wasn’t involved in the study, told Being Patient, “The study also cannot definitively prove that infection initiates disease, rather than accelerates existing pathology.”

Because the study was done in post-mortem tissue, it is impossible to tell when the infection started. “We cannot time-stamp when infection began or definitively classify it as acute versus chronic in each individual,” Koronyo-Hamaoui said. 

There’s a possibility that Alzheimer’s affects immune function and impairs the body’s ability to fight off the bacteria. “In this scenario, infection could be a consequence of Alzheimer’s-related vulnerability rather than its primary cause, a distinction that longitudinal studies will need to clarify,” said Fekrat.

For the researchers, this is only the start of the story. With advances in eye-imaging technology, it might be possible to detect the bacteria in living individuals and test whether it increases the risk of developing the disease. 

“The retina is a direct extension of the brain and shares many of the same cellular and vascular features as the brain,” said Fekrat. “While retinal biomarkers for Alzheimer’s are extremely promising, including those highlighted in this study, most remain in the research phase, and further validation is needed before they can be routinely used in clinical practice.”

The study also opens the door to future trials targeting the bacteria. Previous trials of antiviral medications targeting other chronic infections linked to Alzheimer’s risk, like the herpes virus or gingivitis-causing bacteria, failed to slow the disease. But researchers are hopeful the story could play out differently for C. pneumoniae.