Spouses of Alzheimer's patients are 6 times more likely to develop Alzheimer's themselves. They share daily saliva exchange for decades. Their oral bacteria converges to the same strains. In 2019 Cortexyme published a paper in Science Advances showing Porphyromonas gingivalis, the bacterium behind gum disease, was present in over 90% of postmortem Alzheimer's brains. They also found its DNA in the cerebrospinal fluid of living Alzheimer's patients. P. gingivalis is the keystone pathogen of periodontitis. The CDC says 47% of American adults over 30 have periodontitis right now. The mechanism is specific. P. gingivalis produces enzymes called gingipains. Two types: one cuts proteins at lysine residues, the other at arginine. Tau, the protein that holds your neuronal scaffolding together, is loaded with both amino acids. In cell culture, gingipains shred soluble tau within one hour of infection. The fragments seed the paired helical filaments that become tangles. Tangles are Alzheimer's. Mice fed P. gingivalis through the mouth grew amyloid plaques in their brains. Hippocampal neurons died. The bacteria crossed the blood-brain barrier and started chewing through the same proteins that fail in human Alzheimer's patients. Cortexyme built a drug called atuzaginstat to block gingipains. Phase 1 was clean. They ran a 643-patient Phase 2/3 trial called GAIN. The FDA hit it with a partial clinical hold for liver toxicity. The drug missed both primary endpoints. In August 2022 Cortexyme shut the program down, renamed itself Quince, and pivoted to bone disease. The subgroup with the highest baseline P. gingivalis loads still showed cognitive improvement on secondary endpoints. The bacteria itself kept showing up in postmortem brains across independent studies after the trial closed. Periodontal disease shows up 10 to 20 years before cognitive symptoms in people who later develop Alzheimer's. By the time someone forgets a name, the bacteria has been working for two decades. The intervention point is upstream of your skull.
