Tuesday, July 30, 2013

Misleading microbial headline of the month: Bacteria in Brains Suggest Alzheimer’s-Gum Disease Link

Wow.  Check out this story from Bloomberg: Bacteria in Brains Suggest Alzheimer’s-Gum Disease Link - Bloomberg.  The title suggests that there is some connection between Alzheimer's and Gum Disease.  And so does the story.  Plus check out these other stories:

All based on the same work.  Sounds like a real connection was made in this new work showing a link between bad dental hygiene and Alzheimer's, and also between the bacterium Porphyromonas gingivalis and Alzheimer's.  These would both be a big big deal.  After all - tooth decay is something you can do something about.  And if tooth decay causes Alzheimer's - then - well - we could probably prevent Alzheimer's.

Sounds awesome.  Was going to go invest in companies that are working on this topic.  Then I made a dreadful mistake.  I decided to look at the paper that all of this is based on: Determining the Presence of Periodontopathic Virulence Factors in Short-Term Postmortem Alzheimer's Disease Brain Tissue.

Hmm .. that is weird.  The paper does not seem to have anything in it really closely tied to all the claims in the news stories. Here is the Abstract:
The aim of this study was to establish a link between periodontal disease and Alzheimer's disease (AD) with a view to identifying the major periodontal disease bacteria (Treponema denticola, Tannerella forsythia, and Porphyromonas gingivalis) and/or bacterial components in brain tissue from 12 h postmortem delay. Our request matched 10 AD cases for tissue from Brains for Dementia Research alongside 10 non-AD age-related controls with similar or greater postmortem interval. We exposed SVGp12, an astrocyte cell line, to culture supernatant containing lipopolysaccharide (LPS) from the putative periodontal bacteria P. gingivalis. The challenged SVGp12 cells and cryosections from AD and control brains were immunolabeled and immunoblotted using a battery of antibodies including the anti-P. gingivalis-specific monoclonal antibody. Immunofluorescence labeling demonstrated the SVGp12 cell line was able to adsorb LPS from culture supernatant on its surface membrane; similar labeling was observed in four out of 10 AD cases. Immunoblotting demonstrated bands corresponding to LPS from P. gingivalis in the SVGp12 cell lysate and in the same four AD brain specimens which were positive when screened by immunofluorescence. All controls remained negative throughout while the same four cases were consistently positive for P. gingivalis LPS (p = 0.029). This study confirms that LPS from periodontal bacteria can access the AD brain during life as labeling in the corresponding controls, with equivalent/longer postmortem interval, was absent. Demonstration of a known chronic oral-pathogen-related virulence factor reaching the human brains suggests an inflammatory role in the existing AD pathology.
Alas, even via UC Davis Libraries I do not have access to the full article.  So my inferences will have to be based on the abstract (note to authors, if you want people to judge your full papers not just your abstracts, well, it would be good to have your paper be available).  From what I can tell - what they showed in this paper is that antibodies that are known to find to lipopolysaccharide (LPS) from P. gingivalis showed positive binding to brain material from a few patients who had Alzheimer's and did not show binding to brain material from controls.  So let's ask and try to answer a few questions about this:
  • Does LPS from a specific organism in the brain mean that the organism was in the brain: I don't think so - LPS could move around?
  • Does binding by the antibody they used mean that there is LPS from P. gingivalis there?  Definitely no - there could be cross reactivity with other LPSs or even other molecules?
  • Did they do any more specific tests (e.g., DNA)? Doesn't seem like it.
But let us just assume that they really did detect P. gingivalis in the brains of Alzheimer's patients.  Would this mean PG causes Alzheimer's? Obviously it does not mean that. Let us even assume (ridiculously) that PG causes Alzheimer's.  Would this mean the periodontal disease leads to Alzheimer's? No - PG could come into brains in other ways.

I could go on and on.  There are so so so so so so so many jumps that are needed to go from the limited results presented in this paper to getting anywhere near supporting a hypothesis that periodontal disease causes Alzheimer's that it makes we want to scream.  The news reporting here is awful.  The scientists involved seem to be overhyping their work to extremes with risky, dangerous possible consequences (e.g., - oh - so you have Alzheimer's - it's your fault for not taking care of your teeth ... we need more money for dental care to prevent Alzheimer's; everyone should take prophylactic antibiotics to prevent Alzheimer's and so on).


  1. I can't help but cringe in consternation. The number of times media get it wrong trying to contextualize tentative findings from primary sources is so appalling. The problem is that, media itself can serve as a primary source to many other people and the vicious cycle continues.

    Perhaps the twist is too good to be true that decision makers and fund sources won't bite the bate of this hypothetical link between gum disease and Alzheimer for they know better when it comes to soliciting expert opinions but yes you highlighted the point quite well..

  2. I could send you the PDF if you are interested.

    Apparently I have access through the University of Queensland

    1. please do - jonathan.eisen@gmail.com

    2. thanks for the paper - nothing in there to change what I wrote - the abstract did a decent job of explaining what they did

    3. Could I also get a copy of the PDF? I'd really appreciate it!! jchai924@yahoo.com