Neurodegeneration

Gum Disease Pathogen Fusobacterium nucleatum May Increase Alzheimer’s Risk

Researchers show that the oral pathogen Fusobacterium nucleatum (F. nucleatum) decreases cognitive function and exacerbates Alzheimer's features in mice modeling Alzheimer's.

By Dylan G. Arrazati

Key Points: 

  • The gum disease-assocaited bacteria F. nucleatum lowers cognitive function in mice. 
  • The brain tissue of mice with gum disease exhibit significantly higher levels of amyloid beta (Aβ) and phosphorylated-tau (p-Tau), both hallmarks of Alzheimer’s disease progression. 
  • Mice with gum disease also have elevated brain inflammation. 

The CDC confirms that nearly 50% of adults over the age of 30 have some form of periodontitis, the most prevalent oral inflammatory disease. Periodontitis is linked to a myriad of deadly diseases including cardiovascular disease and Alzheimer’s disease. Research indicates that oral bacteria are responsible for triggering periodontitis, and recent evidence suggests that F. nucleatum, an oral bacteria with strong ties to pregnancy complications, might be a driving force behind Alzheimer’s progression. 

In a new study published in the journal Frontiers in Aging Neuroscience, researchers evaluated the effects of F. nucleatum on Alzheimer’s progression in an Alzheimer’s-mouse model. Wu and colleagues showed that infecting mice with F. nucleatum hampered cognition and boosted the levels of Aβ and p-Tau in the brain tissue of mice. Additionally, they found that infected mice displayed greater levels of brain inflammation than healthy mice, further demonstrating F. nucleatum’s harmful effects on the brain.  

F. Nucleatum Increases Cognitive Impairment

To examine the clinical effects of F. nucleatum on cognitive function, Wu and colleagues conducted a novel object recognition task on mice infected with F. nucleatum. Here, mice were placed in an open box that contained novel objects, and investigators measured the time spent exploring each object. After one and two months, healthy mice spent more time with the novel objects compared to infected mice, indicating that infection with F. nucleatum hampers cognition. 

(Wu et al., 2022 | Frontiers in Aging Neuroscience) F. Nucleatum hampers cognition. Healthy (5XFAD control) and infected (5XFAD F.n) mice underwent a novel recognition task before, and after one and two months. Movement patterns, velocity, distance traveled, and time spent on each novel object were used to calculate a discrimination index score, with higher scores indicating superior recognition and cognition. At baseline, no significant changes were observed. At one and two months after baseline, healthy mice had significantly higher discrimination index scores, indicating that infected mice exhibited cognitive impairment. 

Oral Infection Increases Aβ and p-Tau in Brain Tissue 

Studies show that Alzheimer’s disease manifests through the abnormal accumulation of harmful Aβ proteins, which build up between neurons and impact cognitive function. What’s more, the accumulation of the phosphorylated version of the tau protein (p-Tau) aggregates to form structures called “tangles” that inhibit neuronal communication, another hallmark of Alzheimer’s progression. With this in mind, Wu and colleagues decided to look at the levels of Aβ and p-Tau in the brain tissue of mice. Investigators found that infected mice displayed significantly higher levels of p-Tau than healthy mice. Further results showed that infected mice also exhibited higher levels of Aβ, however, the difference was not statistically significant. Taken together, the findings demonstrate that F. nucleatum potentially contributes to the amplification of Alzheimer’s features. 

(Wu et al., 2022 | Frontiers in Aging Neuroscience) F. Nucleatum increases Aβ and p-Tau. The graph on the left shows the difference in brain Aβ levels between infected (F.n. treated) and healthy (control) mice. Healthy mice seem to have lower Aβ levels, but the difference is not significant. The graph on the right shows the difference in brain p-Tau levels between infected and control mice. The brain tissue of control mice have significantly lower levels of p-Tau. 

F. Nucleatum Raises Brain Inflammation

Microglial cells are the resident immune cells of the central nervous system (CNS) and are critical for the health and maintenance of the CNS. Research shows that over-activation of microglial cells is an early indicator of Alzheimer’s and is responsible for the release of pro-inflammatory molecules like TNF-ɑ and IL-1β into the CNS. Notably, excessive TNF-ɑ and IL-1β secretion have been shown to mediate Aβ accumulation, ultimately leading to more Aβ plaque buildup. 

Wu and colleagues previously confirmed that F. nucleatum promotes microglial activation in culture, so they wanted to see if infecting mice with F. nucleatum also changed the activity of TNF-ɑ and IL-1β. As expected, the brain tissue of healthy mice had drastically lower TNF-ɑ and IL-1β activity than infected mice. Overall, the findings suggest that F. nucleatum exacerbates brain inflammation through microglial activation and secretion of pro-inflammatory molecules. 

(Wu et al., 2022 | Frontiers in Aging Neuroscience) F. nucelatum increases TNF-ɑ and IL-1β. The graph on the left shows the differences in TNF-ɑ levels in the brain tissue of infected-Alzheimer’s mice (5XFAD F.n), uninfected Alzheimer’s mice (5XFAD control), infected healthy mice (Wildtype F.n.), and uninfected healthy  mice (wildtype control). The graph on the right shows the differences in IL-1β levels in brain tissue. 

Don’t Sleep on Oral Hygiene

Although age and genetics play a huge role in determining whether someone is at risk for Alzheimer’s, it appears that the oral pathogen F. nucleatum may be another key player in Alzheimer’s progression. Thus, we should continue striving to consistently maintain good oral hygiene to mitigate Alzhiemer’s progression and improve overall health. Like our parents always told us, make sure to brush your teeth once in the morning and once at night for two minutes and remember to floss after meals. Also, visiting the dentist at least once a year is vital in helping lower the risk of developing unwanted dental issues and potentially Alzheimer’s. 

Model & Dosage

B6 congenic 5XFAD 4-month-old mice

Wildtype B6 mice

100 µL F. nucleatum

 

Source

Wu H, Qiu W, Zhu X, Li X, Xie Z, Carreras I, Dedeoglu A, Van Dyke T, Han YW, Karimbux N, Tu Q, Cheng L and Chen J (2022) The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways. Front. Aging Neurosci. 14:912709. doi: 10.3389/fnagi.2022.912709

 

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