Chlamydia pneumoniae and SARS-CoV-2 infections may play a role in Alzheimer's pathogenesis

A recent review by researchers at Philadelphia College of Osteopathic Medicine (PCOM) shows Chlamydia pneumoniae (Cpn) and SARS-CoV-2 infections may play a role in the pathogenesis of Alzheimer's disease.

Published in Frontiers in Aging Neuroscience, the review highlights that both infections increase levels of substances in the brain called cytokines, especially IL-6 and CCL2, which cause inflammation. This ongoing inflammation can harm brain cells and may help speed up the buildup of harmful proteins linked to Alzheimer's.

The review shows that Cpn and SARS-CoV-2 can invade the central nervous system through both the blood brain barrier and potentially more importantly the olfactory route, which is responsible for our sense of smell. The olfactory system is lined with a specialized neuroepithelium that can serve as an entry point for pathogens to the brain. After initial infection, these microbes can travel along the olfactory nerves, ultimately reaching the brain's olfactory bulbs, which are linked to areas of the brain for memory and cognition. This pathway is particularly relevant given that loss of smell is an early symptom in both COVID-19 and Alzheimer's disease.

The research examined peer-reviewed studies on the associations of Cpn and SARS-CoV-2 with Alzheimer's, coupled with a special consideration for genetic risk factors such as APOEε4, biomarkers (IL-6, CCL2, NRP1), and the structural and functional aspects of infection and neuroinflammation. PCOM researchers documented that individuals carrying this gene variant appear to be more susceptible to both Cpn and SARS-CoV-2 infections, potentially amplifying their risk for developing the disease.

“These findings bring us one step closer to understanding the complex interactions between infections and Alzheimer's disease,” said PCOM's Brian J. Balin, PhD, a professor of Neuroscience and Neuropathology and director of the Center for Chronic Disorders of Aging (CCDA), who co-authored the report. “As we continue to learn more about the role infectious agents play in the development of this disease, we hope to create new avenues for prevention and treatment.”

Balin and his team have dedicated over two decades working under the hypothesis that infectious agents could be a trigger for the process that causes the accumulation of amyloid and tau build-up, which are key indicators of Alzheimer's disease. Most recently, he helped establish PCOM's Pathobiome Research Center to further examine the connections between infectious processes and other chronic disorders in addition to Alzheimer's disease.