Study Unveils New Evidence on the Cause of Alzheimer’s Disease

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A prominent bacterium found in chronic periodontitis has been identified in the brains of patients with Alzheimer’s disease, providing strong evidence connecting P. gingivalis to the development of Alzheimer’s, according to a study published in journal Science Advances.

In a model done on mice, oral P. gingivalis led to increased production of amyloid beta, a component of amyloid plaques commonly associated with Alzheimer’s disease. The team also found the organism’s toxic enzymes, or gingipains, in the neurons of patients with the disease. Gingipains are secreted and transported to outer bacterial membrane surfaces and have been shown to mediate the toxicity of P. gingivalis in a variety of cells.

In attempt to block the neurotoxicity, researchers designed and synthesized small-molecule inhibitors targeting gingipains. In preclinical experiments, researchers demonstrated that gingipain inhibition reduced the bacterial load of an established P. gingivalis brain infection, blocked amyloid beta production, reduced neuroinflammation and rescued neurons in the hippocampus- the part of the brain that mediates memory and frequently deteriorates in the early stages of Alzheimer’s disease.

Jan Potempa, PhD, a researcher in the University of Louisville School of Dentistry’s department of oral immunology and infectious disease, was part of the team of international scientist led by Cortexyme Inc., a privately held, clinical-stage pharmaceutical company.

“An even more notable aspect of this study is demonstration of the potential for a class of molecule therapies targeting major virulence factors to change the trajectory of Alzheimer’s disease, which seems to be epidemiologically and clinically associated with periodontitis,” Dr. Potempa said.

Learn more about this study in Science Advances (2019); doi: 10.1126/sciadv.aau3333.