Could a Cure for Alzheimer’s Disease Lie in the Mouth?

Written by Kacey Haptonstall, MS, Becca Malizia, MS

It’s a wonderful thing when the mentees teach the mentor. My young and talented team combined what they are learning in school with some of the research we do here, enlightening me in the process. Let us know what you think! – DrBonnie360

Alzheimer’s Disease is the sixth leading cause of death among Americans and currently affects 5.8 million people. Similar to autoimmune disease, ⅔ of people with Alzheimer’s in the United States are women. Rates of Alzheimer’s are projected to continue to increase substantially, with estimates indicating nearly 14 million cases by 2050. One of the main problems with Alzheimer’s is that the cause of the disease is unknown and there is no cure.

So what is Alzheimer’s Disease?

Alzheimer’s is the most common form of dementia. It is a neurodegenerative disease that impairs cognitive function and is hallmarked by amyloid-beta plaques, neurofibrillary tangles, and neuronal death. It can only definitively be diagnosed after death, but is usually not the actual cause of death. Most people with Alzheimer’s end up dying of pneumonia or another kind of infection most likely due to their weakened immune system.

Alzheimer's Disease BRAIN
source: wikicommons

It is often diagnosed when a loved one notices severe “forgetfulness,” including misplaced objects, lack of hygiene, or a general mood shift. Alzheimer’s affects thinking, memory, and behavior, interfering with daily life greatly. Alzheimer’s is a progressive disease, meaning it gets worse over time. Eventually, individuals forget how to eat, drink, walk, and often sleep less than a few hours at a time, so they require constant care and attention.

Is Alzheimer’s a disease of civilization?

Map of Alzheimers Disease related deaths
Source: wikipedia

Epidemiological research shows that rates of Alzheimer’s has greatly increased over the last 100 years. The way we live in modern times is vastly different than how we evolved to live. Because of this mismatch, it is possible we are susceptible to diseases that may not have been around in our evolutionary history Alzheimer’s may be one of these. Interestingly enough, the infamous  “Alzheimer’s allele” APOE-4 (E4), is the most ancestral allele — further evidence that we could be experiencing a mismatch with our modern environment.

The change in microbial composition in humans over time

Our change in lifestyle over the course of human history has also affected the microbial buddies that we coevolved with. Major environmental and lifestyle transitions have resulted in a shift in the composition of our microbiomes. A plethora of research has shown that microbial dysbiosis (a change in the normal composition, resulting in imbalance) is connected to diseases and various autoimmune disorders. Whether or not Alzheimer’s is truly an autoimmune disease continues to be debated, but the immune characteristics in Alzheimer’s disease are certainly present.

Alzheimer’s disease and the mouth

Like many autoimmune and other systemic diseases, evidence also supports a link between periodontal disease, tooth loss, and Alzheimer’s Disease. This connection has been shown multiple times, in many different places including, Sweden, Japan, and the state of Wisconsin.

  • A Swedish twin study showed losing more than half of your teeth by 35 was strongly associated with developing Alzheimer’s. [1]
  • A Japanese study found that people who had lost more than half of their teeth by age 50-60 were 2.6 times more likely to get Alzheimer’s. [2]
  • In Wisconsin, US, a study done among nuns showed that having less than ten teeth increased their risk of developing Alzheimer’s 2.2 times that of those with ten or more teeth. [3]

While correlation does not mean causation, it is clear that oral health and oral care are connected to Alzheimer’s disease, and may be very important in shedding light on this elusive disease going forward.

Oral Diseases Graphics
Source: frontiersin.org

Getting into the microbial details, a causation in sight?

Porphyromonas gingivalis (P. gingivalis) the bacteria highly responsible for the development of periodontal disease has recently been implicated in Alzheimer’s Disease. For the first time, a group of researchers in Northern California have been able to suggest causality, not just correlation. After infecting the mice models with P. gingivalis, the bacteria was found in the brain of the mice along with amyloid beta plaques one of the known hallmarks of Alzheimer’s disease. This group, Cortexyme, is currently working on a way to use this new information to create a possible novel therapeutic intervention for Alzheimer’s a molecular inhibitor with the hope of disrupting this harmful connection between the mouth and the brain. [4] Click here to read more about their research and work (see page 88).

Alzheimer’s, diet and periodontal disease

Our modern diets may be influencing and even enhancing our risk for developing Alzheimer’s Disease. Over the course of our long human history, our diets have changed substantially. To read more on how dietary changes have affected our oral health click here.

Dietary changes may be increasing Alzheimer’s risk through changes in the microbial composition in the mouth. Eating processed and sugary foods creates an environment for harmful bacteria, such as P. gingivalis, to thrive. Accumulation of harmful bacteria can cause mouth dysbiosis, which can subsequently lead to periodontal disease. Check out our article on dietary tips for a healthy mouth.

Bad vs Good Diet to cure Alzheimer's

Did our hunter-gatherer ancestors get periodontal disease?

Evidence from the archaeological record shows that periodontal disease is relatively new in human history, emerging around the time of the Agricultural Revolution (roughly 10-12,000 years ago) and then escalating during the Industrial Revolution (roughly 200 years ago). Tooth decay and periodontal disease are rare in archaeological samples from hunter-gatherer populations but can be seen throughout the transition to agriculture. [5] 

P. gingivalis was not found in the dental remains of pre-agricultural revolution hunter-gatherers, but is found in the dental remains of farming communities post agricultural revolution. This coincides with increased occurrences of periodontal disease. Similarly, another microbe associated with Alzheimer’s disease, Treponema, seemingly emerged in the oral microbiome during this time period as well. The industrial revolution brought an influx of processed and refined sugars which has been associated with enamel demineralization, dental caries, and eventual tooth loss ALL of which have been associated with Alzheimer’s disease.

The future of Alzheimer’s research

The oral microbiome, in general, has been very understudied, but it is an up-and-coming field in microbiology, immunology, and evolutionary medicine. It’s easy to obtain samples, sequencing is becoming more accessible, and there is a very real possibility for treatment available here.

The future for Alzheimer’s seems much brighter if we continue to research and expand our knowledge surrounding the oral microbiome and oral health.

Click here for more information on current research being done on the oral microbiome and Alzheimer’s!


References:

  1. Gatz M, Mortimer JA, Fratiglioni L, Johansson B, Berg S, Reynolds CA, Pedersen NL. 2006 Potentially modifiable risk factors for dementia in identical twins. Alzheimers Dement 2, 110–117. (doi:10.1016/j.jalz.2006.01.002)
  2. Kondo K, Niino M, Shido K. 1994 A case-control study of Alzheimer’s disease in Japan–significance of life-styles. Dementia 5, 314–326.
  3. Stein PS, Desrosiers M, Donegan SJ, Yepes JF, Kryscio RJ. 2007 Tooth loss, dementia and neuropathology in the Nun study. J Am Dent Assoc 138, 1314–1322; quiz 1381–1382.
  4. Dominy SS et al. 2019 Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science Advances 5, eaau3333. (doi:10.1126/sciadv.aau3333)
  5. Adler CJ et al. 2013 Sequencing ancient calcified dental plaque shows changes in oral microbiota with dietary shifts of the Neolithic and Industrial revolutions. Nature Genetics 45, 450–455. (doi:10.1038/ng.2536)

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