Alzheimer’s disease is the most common type of dementia in the UK, affecting one in six over 80, and is defined as ‘progressive mental deterioration, due to generalised degeneration of the brain’. Symptoms include memory loss and confusion, that sadly we’ve seen in so many of our elders. However, a recent study published in the scientific journal Science Advances has implied that infection with the bacteria (Porphyromonas gingivalis), commonly found in gum disease, is thought to be the underlying cause of Alzheimer’s disease. As a result of this breakthrough, scientists now believe there is potential to design a new drug, which inhibits the action of this bacteria to reduce the devastating effects of Alzheimer’s. Therefore, could this latest discovery be the key to curing one of the world’s most common diseases?
P. gingivalis is a gram-negative bacterium that causes chronic periodontitis, an inflammatory disease that destroys gums supporting the tooth, and can therefore lead to tooth loss. However, in this study scientists were investigating if this bacterium was also responsible for the development of Aβ (Amyloid-beta) plaques, which would indicate the bacteria was linked with Alzheimer’s.
In order to see if there was correlation between the presence of the bacteria and the development of Alzheimer’s in humans, the scientists initially investigated if this correlation occurred in mice. The scientists firstly tested the effect of introducing the bacteria into a mouse that had been previously genetically modified to produce proteins found in Alzheimer’s disease. This resulted in brain infection and activation of the complement pathway, and inflammatory immune response, both of which are thought to be involved in Alzheimer’s Disease.
Another type of mouse was also tested, which was mutated to promote the deposition of Aβ like plaques, which results showed lead to the formation of oligomers. These oligomers are extremely toxic and causative agents in the development of Alzheimer’s. Therefore, the results of these experiments have led scientists to believe that there is a strong correlation between the presence of P. gingivalis and Alzheimer’s.
An additional experiment in the study looked at the levels of major virulence factors, known as gingipains, produced by P. gingivalis in the brains of both healthy and Alzheimer’s patients. Gingipains are known to mediate the bacteria’s toxicity, and therefore promotes neuronal damage in the brain which ultimately leads to Alzheimer’s. Levels of gingipain were detected by gingipain-specific antibodies (CAB101 and CAB102), which bind to the gingipain, and therefore the amount of gingipain present could be detected based on the amount of antibody that was bound.
The results implied that in Alzheimer’s patients, gingipains were often highly prevalent, with 96% of the samples having CAB101 bound and 91% of samples having CAB102 bound. The results of this experiment have not only further cemented the hypothesis that the presence of P. gingivalis (particularly the gingipain component) is linked to the development of Alzheimer’s but could also be used in the future to develop a much-needed method of diagnosing patients with Alzheimer’s disease.
But what is the significance of discovering this key component in the causation of Alzheimer’s? As a result of discovering the specific factor within the P. gingivalis thought to be linked with the development of Alzheimer’s, scientists have started creating a drug which can inhibit its activity. The drug is designed to be potent, selective and brain penetrant, and so can access areas of the brain that are usually afflicted by Alzheimer’s disease.
Furthermore, initial experiments using the drug have shown findings that gingipain inhibition reduced many of the factors associated with Alzheimer’s. These included overall reduction in bacterial load and plaque production, as well as reduced neuroinflammation and an increase in rescued neurons in the hippocampus (the region in the brain that is often affected first by Alzheimer’s, which in turn causes the all too familiar long-term memory loss).
As a result of these extremely positive findings, it looks like scientists could well be on the way to at the least delaying one of the world’s most prevalent diseases. The question is, will the newly designed drug make it all the way production for humans? Or, is it all too good to be true?