Link between Alzheimer’s disease and periodontal bacteria gains traction

Written by Sharon Salt (Editor)

A recently published study in Science Advances has suggested a link between periodontal bacteria (Porphyromonas gingivalis) and Alzheimer’s disease (AD). Although periodontal bacteria have been indicated in the development and progression of AD before, this new study has hit the headlines due to implications that gingipain (a toxic protease released by the bacteria) inhibitors may be used to treat P. gingivalis and neurodegeneration in AD.
Within the study, investigators from Cortexyme (CA, USA) examined brain tissue from people with Alzheimer’s and compared them with healthy control subjects. The findings revealed that the bacteria were detected in almost every sample they examined, regardless of whether the individual had AD.

However, the levels of bacteria themselves did not seem to be different in AD patients compared with healthy controls. It’s important to note that small numbers were reported on: three Alzheimer’s patients and six controls.

In addition to this, a larger experiment that examined gingipain in approximately 100 individuals showed an increase in bacterial proteins in AD cases compared to controls. Treatment with the company’s experimental drug in mice also demonstrated that the drug reduces the increase of amyloid when the mice were infected with P. gingivalis.

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Speaking about the study, Professor Tara Spires-Jones (University of Edinburgh, UK) mentions: “It is worth noting that P. gingivalis bacterial proteins were found in healthy people and some people with AD did not have increased levels compared to these controls. People with AD also have disruption of their blood–brain barrier, making them more susceptible to getting infections in their brains, so while these data are interesting, it is possible that the infection is a by-product instead of a cause of disease.”

“The data from mice in this paper show small increases in the levels of one of the Alzheimer’s-associated proteins with P. gingivalis infection that were prevented with the experimental drug, but these mice did not develop any Alzheimer’s pathology and were conducted in small groups (around ten mice per group).”

Spires-Jones added: “So it’s great news that a recent trial by this company showed this drug is safe in people and this study provides some evidence that it may affect Alzheimer’s-related proteins; however, we will have to await the larger clinical trial to see if it will be beneficial to people living with Alzheimer’s disease.”

David Reynold, Chief Scientific Officer from Alzheimer’s Research UK (Cambridge, UK), concluded: “It’s important we carefully assess all new potential treatments, and this drug is currently in an early phase clinical trial to establish if it is safe for people. We will have to see the outcome of this ongoing trial before we know more about its potential as a treatment for Alzheimer’s.”

Sources: Dominy SS, Lynch C, Ermini F et al. Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci. Adv. 5(1), eaau3333 (2019); Press release: www.uoflnews.com/releases/new-science-bacterial-pathogen/; www.sciencemediacentre.org/expert-reaction-to-study-looking-at-alzheimers-disease-and-a-bacterium-that-causes-gum-disease/