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Gum Disease Strongly Implicated in Alzheimer’s
Gum infection may play a central role in the development of Alzheimer’s disease (AD), new research suggests.
A multinational team of investigators carried out a series of experiments to examine the potential impact of Porphyromonas gingivalis, the major pathogen of chronic periodontitis, on AD development. They studied mouse models as well as examined the cerebrospinal fluid (CSF) and postmortem brain tissue of individuals with AD.
The presence of oral P gingivalis infection in mice resulted in brain infiltration by the bacteria that was accompanied by increased production of Aβ1-42, a component of amyloid plaques implicated in AD.
Gingipains were also found to damage tau, a protein necessary for normal neuronal function and whose disruption is likewise implicated in AD.
Moreover, DNA from P gingivalis was found in the CSF of living AD patients and in postmortem studies of AD patients.
Small molecule gingipain inhibitors administered to mice reduced the bacterial load of P gingivalis in the brain, blocked Aβ1-42 production, reduced neuroinflammation, and rescued hippocampal neurons in mice.
“Our findings indicate that there is a significantly increased load of gingipains, cysteine protease virulence factors secreted by P gingivalis, in the brain of AD patients, when compared to nondemented controls,” said lead author Stephen Dominy, MD, chief scientific officer of Cortexyme, the company that funded the study.
“We demonstrate in the paper that these pathological effects can be blocked by gingipain inhibitors in wild-type mice, providing a new strategy for Alzheimer’s treatment by specifically targeting P gingivalis and gingipains instead of Aβ or other downstream pathways,” he said.
The study was published online January 23 in Science Advances.
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