Common pneumonia bacterium may fuel Alzheimer’s disease

For the first time, scientists showed that Chlamydia pneumoniae can travel to the retina, the light sensitive tissue at the back of the eye. Once there, it activates immune responses that are tied to inflammation, loss of nerve cells, and declining cognitive function.

"Seeing Chlamydia pneumoniae consistently across human tissues, cell cultures and animal models allowed us to identify a previously unrecognized link between bacterial infection, inflammation and neurodegeneration," said Maya Koronyo-Hamaoui, PhD, professor of Neurosurgery, Neurology, and Biomedical Sciences at Cedars-Sinai Health Sciences University and the leading, senior author of the study. "The eye is a surrogate for the brain, and this study shows that retinal bacterial infection and chronic inflammation can reflect brain pathology and predict disease status, supporting retinal imaging as a noninvasive way to identify people at risk for Alzheimer's."

Higher Bacterial Levels Tied to Cognitive Decline

The research team analyzed retinal tissue from 104 people using advanced imaging, genetic testing, and protein studies. Participants included individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease.

People diagnosed with Alzheimer's had much higher levels of Chlamydia pneumoniae in both their retinas and brains compared to those with normal cognition. Researchers also observed that greater amounts of the bacterium were associated with more severe brain damage and worse cognitive decline.

Elevated bacterial levels were especially common in individuals carrying the APOE4 gene variant, which is known to increase the risk of developing Alzheimer's.

Infection May Accelerate Alzheimer's Processes

To further test the connection, scientists examined human nerve cells in the lab and studied mice with Alzheimer's disease. In both models, infection with Chlamydia pneumoniae led to increased inflammation, greater nerve cell death, and worsening cognitive problems. The infection also stimulated the production of amyloid-beta, the protein that builds up in the brains of people with Alzheimer's.

The study was led in part by co-first authors Bhakta Gaire, PhD, and Yosef Koronyo, MSc.

"This discovery raises the possibility of targeting the infection-inflammation axis to treat Alzheimer's," said Timothy Crother, PhD, co-corresponding author of the study and research professor at Cedars-Sinai Guerin Children's and the Department of Biomedical Sciences at Cedars-Sinai.

Overall, the findings indicate that treating long standing bacterial infections and the inflammation they cause could represent a new therapeutic approach. The results also strengthen the case for using the retina as a noninvasive tool to help detect and monitor Alzheimer's disease.

Additional Cedars-Sinai authors include Bhakta Gaire, Yosef Koronyo, Jean-Philippe Vit, Alexandre Hutton, Lalita Subedi, Dieu-Trang Fuchs, Natalie Swerdlow, Altan Rentsendorj, Saba Shahin, Daisy Martinon, Edward Robinson, Alexander V. Ljubimov, Keith L. Black, Jesse Meyer, and Moshe Arditi.

Other authors include Julie A. Schneider, Lon S. Schneider, Debra Hawes, Stuart L. Graham, Vivek K. Gupta, and Mehdi Mirzaei.

Funding: This work has been supported by the NIH/NIA grants R01AG056478, R01AG055865, and AG056478-04S1 (M.K.H.), R01AG075998 (M.K.H. and T.R.C.), and Alzheimer's Association grant AARG-NTF-21-846586 (T.R.C.). MKH is also supported by The Goldrich and Snyder Foundations. ER has been supported by The Ray Charles Foundation.