In January of 2019, the internet was hit with another case of fact-or-fiction when a small biotech startup in San Francisco revealed that infectious diseases may lead to the development of Alzheimer's Disease (2). Stephen Dominy, a psychiatrist and the co-founder of Cortexyme Inc, revealed that the idea came many years ago when he was treating people with HIV at the University of California, San Francisco. He noticed that some of the patients who had HIV-related dementia recovered their memory after taking antiviral drugs. This similar concept propelled him to look seriously at the P. gingivitis infection and its relationship with Alzhiemer’s. The team specifically focused on gingipains (an enzyme released from the bacteria P gingivitis) and discovered an abundance of it in the brain tissue of deceased patients with Alzheimer’s. After research that extended between the United States and labs in Europe, New Zealand, and Australia, the Cortexyme team was able to confirm that a bacterium does exist in the spinal fluid of living patients and that over 90% of the Alzheimer's brain samples had the bacteria present had higher quantities of tau and ubiquitin proteins (whose accumulation are strongly linked to Alzheimer's) (1).
Although the finding presents a strong correlation, it still leaves many skeptics questioning whether this conclusion is a scientifically solid cause or simply circumstantial evidence. Dr. James M. Noble of the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University Medical Center questions whether an elderly patient’s oral health is an independent risk factor (3). After all, the P. gingivitis bacteria is present in everyone with more than 90% of persons 13 years of age or older exhibiting it (7). However, to explore whether this disease was a contributing factor to the development of Alzheimer's, a team from the University of Illinois furthered their research on another specimen: mice.
To remove the lurking variable of age from this finding, the team swabbed the gums of healthy young mice with P. Gingivitis every other day through the course of 6 weeks to establish an infection. The data collected detected the bacteria in the mice’s brains alongside abnormally high levels of beta-amyloid protein, another protein adjacent to tau that accumulates in Alzheimer's patients (1).
While the discovery answers some questions, it also serves as a potential stepping stone into pharmaceutical solutions for Alzhiemer’s. Cortexyme reports that their trial-drug COR388 is currently in the first phase of clinical trials to block P. Gingivitis from creating amyloid plaques in the brain (4). The preclinical studies of the drug have found it to decrease bacterial load of P. Gingivitis and block excessive production of both proteins, which reduces neuroinflammation and protects the neurons in the hippocampus (6). The firm is now concentrating on developing a 2 year trial on this drug and is building a research team to work towards developing a vaccine in the near future (5).
So for the time being, it’s back to the basics. I personally recommend the classic “Brush Your Teeth Song” and some Colgate to start!
References:
- “Gum Disease-Causing Bacteria could Spur Alzheimer's”. ScienceMag.org
KaiserJan, Jocelyn, et al. “Gum Disease–Causing Bacteria Could Spur Alzheimer's.” Science, 5 Feb. 2019, www.sciencemag.org/news/2019/01/gum-disease-causing-bacteria-could-spur-alzheimer-s.
- “How Gum Disease could Lead to Alzheimer’s”. Medical News Today
Cohut, Maria. “How Gum Disease Could Lead to Alzheimer's.” Medical News Today, MediLexicon International, 26 Jan. 2019, www.medicalnewstoday.com/articles/324298.php.
- “Gum Disease may signal faster Alzheimer’s decline”. Reuters
Doyle, Kathryn. “Gum Disease May Signal Faster Alzheimer's Decline.” Reuters, Thomson Reuters, 15 Mar. 2016, www.reuters.com/article/us-health-dementia-gum-disease-idUSKCN0WH2UU.
- “Experimental Alzheimer's Drug Targets Gum Disease Bacteria”. New Scientist
Wilson, Clare. “Experimental Alzheimer's Drug Targets Gum Disease Bacteria.” New Scientist, www.newscientist.com/article/2210245-experimental-alzheimers-drug-targets-gum-disease-bacteria/.
- “Gum Disease and Alzheimer's: How Bacteria Travels Through the Brain”. Being Patient
“Gum Disease and Alzheimer's: What Does the Evidence Show?” Being Patient,
11 Apr. 2019, www.beingpatient.com/gum-disease-alzheimers-2/.
(6) Ndivya. “Cortexyme Initiates New Trial of Alzheimer's Medicine.” Drug Development
Technology, 17 Apr. 2019, www.drugdevelopment-technology.com/news/cortexyme-alzheimers-trial/.
(7) McClellan, D L, et al. “Age and Prevalence of Porphyromonas Gingivalis in Children.”
Journal of Clinical Microbiology, U.S. National Library of Medicine, Aug. 1996,
www.ncbi.nlm.nih.gov/pmc/articles/PMC229175/.