The case for porphyromonas gingivalis as the cause of Alzheimer's disease gets stronger ... a lot stronger

In Beating the Dementia Monster we wrote about a connection between gum disease and Alzheimer's disease.  We noted that some believe gum disease is the cause of Alzheimer's disease, and defeating gum disease should defeat Alzheimer's disease.  This is hard to believe, considering all of the dynamics around how the disease develops and progresses.  But there's some new research findings that at least reinforce our understanding of some kind of strong connection between the bacterium p. gingivalis and the disease.  In fact, there is growing evidence that beta amyloid, considered a culprit in development of Alzheimer's disease is, in fact, part of the body's mechanism for keeping p. gingivalis from damaging brain cells.

In January 2021, we wrote about a new treatment candidate, atuzaginstat, that we hoped would be an effective antibiotic treatment against p. gingivalis.   We wrote that it had begun a phase 2/3 trial and had then passed an important milestone.  We looked forward to final results in December 2021.

While December isn't here yet, good news continues to come from the ongoing trial, sponsored by the pharmaceutical company, Cortexyme.  The news is that, among the 230 Alzheimer's patients selected as current phase test subjects, 100% showed evidence of p. gingivalis infection in their cerebrospinal fluid (CSF).  I don't know what other surveys have been done to associate antibodies and other biomarkers for p. gingivalis in CSF, but this certainly shows that the association is really, really common.  

Does that mean that killing off all of the p. gingivalis will reverse Alzheimer's disease?  That remains to be seen.  However, other research finds that the greater the p. gingivalis infection, the faster the cognitive decline.  This suggests that controlling the infection may control the rate of decline.

In late August, the pharmaceutical industry held it's annual Biomarkers for Alzheimer’s Disease Summit (online).  During the summit, Leslie Holsinger, Executive Vice President, Research and Development at Cortexyme, Inc. presented the status of the trial and discussed the significance of what's been learned so far.  Her presentation slides are here.  To me, the most interesting information was the graph on page 7 relating the speed of cognitive decline to the severity of gum infection. 

Also fascinating is the graphic on page 8 showing Cortexyme's understanding of disease progression from initial gum infection, to infiltration of the brain by the bacterium, the secretion of gingipains by the p. gingivalis, the mischief the gingipains cause, fragmentation of tau proteins (as we discussed in Beating the Dementia Monster), the involvement of ApoE proteins (from the famous "Alzheimer's gene"), and finally the body's response via beta amyloid production and inflammation.

Page 19 had some interesting test results for a female Alzheimer's disease patient from the now-complete phase 1 study.  It was a test I am familiar with in which the test subject must explain what they see in a picture.  After 28 days of treatment, the improvement is obvious.  Of course, that's just one person, but who knows what more we'll learn from the current trial?

So ... moral of the story?  Floss your teeth!