Could gum disease be the cause of Alzheimer’s disease?

Joan Joe. 11/27/2020.


Alzheimer's disease is a progressive condition that causes the degeneration and death of brain cells. (PMLiVE)


According to the National Institutes of Health (NIH), Alzheimer’s disease is the most prevalent type of dementia, affecting more than 5.5 million Americans. Abnormal protein accumulation, called amyloid plaques and tau tangles, steadily kill brain cells and the connections between them in the brains of people with Alzheimer’s, hindering the capacity of individuals to think and remember. The effects are permanent, and there is no treatment yet for Alzheimer’s. To find one, scientists worldwide are working in high gear, but most medicines that have entered clinical trials have failed.

The difference between a healthy brain and a brain with Alzheimer’s disease (Life Extension Advocacy Foundation)


There are two types of Alzheimer’s: early-onset and late-onset.

Typically, early-onset Alzheimer’s affects individuals before age 65, with the signs typically occurring in a person’s 40s or 50s. According to Mayo Clinic, this type of disorder is rare, affecting only 5% of all people with Alzheimer’s. It is a direct result of hereditary mutations in one of the three genes: APP, PSEN1 or PSEN2. What researchers have discovered from these unusual mutations that cause early-onset Alzheimer’s is that the mutation of the gene leads to the overproduction of a rogue, harmful beta-amyloid protein. The beta-amyloid build-up in the brain develops plaques that are one of the disease’s hallmarks. Just as plaques in the arteries can affect the heart, plaques in the brain can have dire effects on the function of the brain. For the disease to manifest, a person needs to inherit only one of these genes from one parent.


The image models an amyloid-beta protein. (Jeff Brender)


However, the vast majority of Alzheimer’s cases are the late-onset type, which usually affects individuals over 65 years of age. Alzheimer’s late-onset condition is not usually inherited; instead, it is likely to be derived from a combination of genetic, environmental and lifestyle causes. It is believed that a mutation in a gene called ApoE raises the likelihood of a person developing late-onset Alzheimer’s, but does not cause it. According to the NIH, ApoE affects how cholesterol flows through the blood. Research indicates that there is an increased risk of developing Alzheimer’s in people with elevated blood pressure and high cholesterol. Radiation, concussions, injuries and exposure to some contaminants are possible environmental factors.

So, what is the cause of Alzheimer’s disease?

Headlines of revolutionary news have reverberated through the network in recent years- Alzheimer’s disease is not just a disease, it’s an infection.

The hypothesis that bacterial or viral infections could play a role in Alzheimer’s development was unpopularized until about a year ago. However, recently, as scientists have worked out potential pathways for how an infection could lead to the development of these irregular protein buildups in the brain, this concept has gained traction.

Researchers announced the discovery of Porphyromonas gingivalis – the pathogen behind chronic periodontitis, or gum disease – in the brains of deceased Alzheimer’s patients, in a paper led by senior author Jan Potempa, a microbiologist from the University of Louisville. Although experts are still trying to isolate the exact causes of this illness, a litany of papers argues that the deadly spread of Alzheimer’s goes far beyond what we used to think.

The report that spurred the headlines was published in the journal Science Advances. It was reported that gum disease could be a cause of Alzheimer’s. It’s not the first time that the two variables have been related, but the researchers have gone further. Oral infection with the pathogen led to brain colonization by bacteria in separate experiments with mice, along with increased development of amyloid-beta (Aβ), a sticky protein usually associated with Alzheimer’s. Additionally, in the brains of Alzheimer’s patients, the team identified toxic enzymes called gingipains secreted by bacteria. But these tests were conducted after the patients have been deceased. In other words, although P. gingivalis and the disease have been related before, it has never been known whether gum disease causes Alzheimer’s, or whether dementia leads to poor oral treatment.


P. gingivalis' gingipains (red) are among neurons in the brain of a patient with Alzheimer's. (Science Alert)


The researchers write in their paper that their discovery of gingipain antigens in the brains of people with AD and also with AD pathology indicates that a P. gingivalis brain infection is not a consequence of late-stage disease, but rather an early occurrence. This may explain the pathology observed before cognitive impairment in middle-aged people.

Many experiments have been performed on mice looking at late-stage Alzheimer’s; some have been successful, some have not. Cortexyme, a clinical-stage biopharmaceutical company, is currently advancing its lead therapeutic candidate, Atuzaginstat (COR388), in the GAIN Trial (an ongoing Phase 2/3 clinical trial in patients with mild to moderate Alzheimer’s disease). In experiments with mice, COR388 showed that it could minimize the bacterial load of existing brain infection with P. gingivalis while also reducing the development of amyloid-beta and neuroinflammation (inflammation of the nervous tissue).

However, in humans, even the successful ones have failed. From 1998 to 2017, there were around 146 unsuccessful attempts to develop Alzheimer’s medications, and another half-dozen or so were registered in 2018. A drug, Crenezumab seemed successful, but the interim review indicated that the drug was unlikely to reach the primary endpoint of the Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score improvement from baseline. So the tests conducted in mice shouldn’t yet be considered as proof that it is a cause.

Many scientists in this area expect that they will soon discover that the causes of Alzheimer’s are vast. While most medications that have been developed to target Alzheimer’s have failed early in clinical trials, there are still many trials underway, and more to come in the future. Scientists expect that they will soon discover that Alzheimer’s causes are many and believe that we are entering the golden age of Alzheimer’s research.

So what can we do?

According to the Centers for Disease Control and Prevention, there is growing evidence that physical, mental and social behaviors decrease the likelihood of developing Alzheimer’s. The ability to reliably track memory and other cognitive functions in later life is a crucial factor in avoiding the onset of impairment of Alzheimer’s and other dementias. CANTAB Mobile is a diagnostic software available to GPs that is easy to use to objectively test memory in older adults who are concerned about their risk of dementia. For now, individuals should lead a healthier lifestyle to lower their risk of contracting the disease.

Cover Photo: (Gates Notes)


Joan Joe
Joan is a freshman in St. Antony’s Public School, India. She is intrigued by psychology and neuroscience and aspires to join research in neuroscience and STEM-related works. She hopes to help others pursue their passion for STEM through her platform. In her free time, she plays the piano, sings, and loves to read Dan Brown’s books.