Study Discovers An Oral Bacterial Connection To Alzheimer’s Progression

New Research Links Gum Disease Bacteria to Alzheimer’s Disease Progression

A recent scientific investigation has found that a bacterium commonly associated with chronic gum disease may play a role in the development and progression of Alzheimer’s disease (AD). This progressive neurodegenerative condition, which primarily affects memory and cognition, is now being examined through a new lens—oral health.

The bacterium in question is Porphyromonas gingivalis (Pg), known for its role in periodontal disease. The discovery adds another potential factor to the complex web of genetics, environmental influences, and lifestyle choices that contribute to Alzheimer’s onset.

Surprising Findings from International Research Collaboration

The study was spearheaded by Cortexyme Inc., a clinical-stage pharmaceutical company, in partnership with global scientists, and published in Science Advances. While not definitive proof of causation, the presence of P. gingivalis in the brains of Alzheimer’s patients suggests a strong association.

Dr. Jan Potempa from the University of Louisville’s School of Dentistry, a co-author of the study, remarked that the findings offer compelling evidence connecting oral bacteria to the pathogenesis of AD. “Though we’re not declaring P. gingivalis the sole cause, this study provides a valuable foundation to explore new therapeutic approaches,” he said, as reported by Science Daily.

How Oral Bacteria May Influence Alzheimer’s Pathology

Animal testing played a vital role in exploring the connection. When infected with P. gingivalis, the bacteria migrated to the brain and triggered the overproduction of amyloid-beta (Aβ)—a protein known to form the plaques commonly found in Alzheimer’s patients. These amyloid plaques are strongly linked to the degeneration of neurons and brain tissue.

Moreover, researchers identified the presence of gingipains, a group of toxic enzymes produced exclusively by P. gingivalis. These enzymes were found to interact with key brain proteins, including tau (essential for neuron stability) and ubiquitin (which manages damaged proteins), potentially accelerating neural damage.

Targeted Therapy: A New Direction in Alzheimer’s Treatment

Cortexyme utilized these findings to develop a potential treatment targeting the bacterial root of Alzheimer’s. Their approach involved designing small molecule inhibitors to block the activity of P. gingivalis enzymes, especially gingipains.

One compound, known as COR388, showed early promise in preclinical studies by significantly reducing both bacterial load and associated brain inflammation. It also lowered levels of Aβ42, a variant of amyloid-beta, offering protection to neurons in the hippocampus—a critical area of the brain involved in memory and one of the first regions to be affected by Alzheimer’s.

Following the positive outcomes from preclinical work, Cortexyme launched a Phase 1b human trial. Results, presented at the 11th Clinical Trials in Alzheimer’s Disease Conference in October 2018, revealed that patients treated with COR388 exhibited noticeable improvements in cognitive function.

Encouraged by these findings, the company moved forward with its Phase 2 and Phase 3 trials starting in 2019, with the aim of validating COR388 as a novel therapeutic agent in the battle against Alzheimer’s.

Conclusion:
While more evidence is needed before establishing a direct causal link, this research underscores the emerging connection between oral health and neurodegenerative disease. If confirmed, it could revolutionize both the understanding and treatment of Alzheimer’s, introducing antibacterial strategies as a key component of cognitive health preservation.