For many decades, there have been intense research efforts aimed at understanding and treating Alzheimer’s disease (AD). The results have been disappointing. I think that if anyone had told me back in the 1980s that well into the 2020s we would still not have an effective treatment for the disease—or even really understand what is causing it—I probably would not have believed them. But here we are. The good news is that the search for contributing factors driving AD has broadened beyond “plaques and tangles,” and some of the factors identified might be a bit surprising to the old guard.
The paper by Rozenblum et al. details the evidence that microbes from the mouth likely contribute to the pathophysiology of Alzheimer’s disease, what the mechanisms of their roles might be, and how we can use this knowledge to screen for people at risk for AD. Key highlights include:
- Oral dysbiosis and overgrowth of pro-inflammatory bacteria are reliably associated with AD.
- Several studies have found evidence for the presence of “oral pathobionts” (microbes that are not inherently beneficial but do not cause disease unless they overgrow) in both oral and brain tissue of people who had AD.
- One pathobiont that is receiving a lot of attention in relation to AD is Porphyromonas gingivalis. P. gingivalis is a “keystone periodontitis pathogen” that produces enzymes called gingipains, which can break down proteins. Gingipains can promote neuroinflammation and other pathophysiological hallmarks of AD, including plaques and tangles. P. gingivalis is consistently found in the brains of individuals with AD. There are several other bacterial species associated with both periodontitis and AD as well.
- In addition to the overgrowth of pathogenic oral bacteria in AD, there is a concomitant decrease in “beneficial” species found among the oral microbiota of people with AD. This may facilitate the overgrowth and “dominance of pro-inflammatory pathogens” that could drive “systemic inflammation linked to neurodegeneration.”
- Oral dysbiosis is also seen in other disorders, including diabetes, hypertension, and kidney disease, which are themselves risk factors for AD.
- The authors point out that “lifestyle interventions remain a cornerstone of oral microbiota modulation, with improved oral hygiene practices and dietary modifications showing systemic benefits. Regular professional dental care, proper brushing techniques, and the use of antimicrobial mouthwashes can significantly reduce pathogenic bacterial loads. Dietary interventions rich in polyphenols, omega-3 fatty acids, and fiber may also foster a healthier oral microbiota while concurrently reducing inflammation, a strategy that aligns with emerging research on the gut–brain axis.” Couldn’t have said it better myself!