A bug about Alzheimer’s

Cortexyme offers a new MOA in Alzheimer’s, faces down skeptics

Cortexyme Inc. believes it has connected the dots between Alzheimer’s and gum disease, outlining a path from the bacteria that cause periodontitis to chronic brain infection with hallmarks of AD. But in a field that has struggled for unity on a causal mechanism, skeptics argue the company’s hypothesis leaves too many unanswered questions, and will hit the same clinical hurdles that have confounded β-amyloid inhibitors.

In a Science Advances study published last month, Cortexyme and collaborators from eight academic institutions offered a new explanation for the etiology of AD, suggesting it stems from proteolytic enzymes released in the brain by Porphyromonas gingivalis.

A constellation of hypotheses for AD have been put forward, centered around β-amyloid and tau, with varying other targets proposed to play a role inside and outside those pathways (see “After Amyloid”.)

The idea of a pathogenic trigger dates to the disease’s origin in the early 1900s. But while the literature contains numerous studies identifying pathogens that correlate with AD, there have been no convincing papers showing a causal connection.

Cortexyme’s paper both corroborated a previously reported link between gum disease and AD in humans and connected the two mechanistically, via experiments in cells and mice.

The study showed oral infection with P. gingivalis in

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