P. gingivalis in Alzheimer's disease brains | Hacker News Reader

P. gingivalis in Alzheimer's disease brains

advances.sciencemag.org

176 pointsAnkaios49 comments

>Transient bacteremia of P. gingivalis can occur during common activities such as brushing, flossing, and chewing, as well as during dental procedures (19), resulting in documented translocation to a variety of tissues including coronary arteries (20), placenta (21), and liver (22). A recent study found that 100% of patients with cardiovascular disease had P. gingivalis arterial colonization

That’s extremely interesting. 100% of patients with heart disease.

I’ve heard flossing may help prevent alzheimers, due to fighting gum disease. This article talks about translocation. Once bacteria has made it into the body, is it too late for gums to have any effect? Or is it more like a total bacterial load: if the gums are continuing to infect the body, the other parts of the body must fight harder to keep the invading bacteria at bay?

Edit: of course, we should know how many patients of a similar age without heart disease had p. Gingivalis in their arteries

> [...] is it too late for gums to have any effect? Or is it more like a total bacterial load [...]

Probably the latter (from the article):

""" A prospective observational study of [Alzheimer Disease (AD)] patients with active [Chronic Periodontis (CP)] reported a notable decline in cognition (Alzheimer’s Disease Assessment Scale—Cognitive and Mini Mental State Examination scales) over a 6-month period compared to AD patients without active CP """

The outcome of this study is effectively meaningless because we don't know how common p. Gingivalis is in the general population's arteries.

I looked elsewhere in the paper and they said:

>P. gingivalis is mainly found during gingival and periodontal infections; however, it can also be found at low levels in 25% of healthy individuals with no oral disease (18).

>I’ve heard flossing may help prevent alzheimers, due to fighting gum disease.

I've heard flossing is only peddled by floss companies, with no real studies to recommend it.

Not sure the jury is out:

https://www.bbc.com/news/health-36962667

I think its a hard case to sell that there is no benefit to oral health by flossing. I know for myself, food gets stuck in places that not even brushing and using mouth wash can dislodge. I dont want to be one of those 'i am a corner case and you are wrong people', but I find it doubtful this is unique to me

I asked my dentist, he told me current consensus leans towards brushing + toothpicks being the best, but flossing + brushing is better than just brushing.

Flossing also takes decent technique to be effective. Simply inserting and removing floss while better than nothing is only so effective.

I can tell you it helps me a lot. After going months without flossing, then transitioning to regular flossing, my gums were subjectively in much better shape. I suppose less sugary food choices could have affected results.

Similarly, for an evidence based investigation into routine 'scale and polish':

> Objective 1: Scale and polish versus no scale and polish Only one trial provided data for the comparison between scale and polish versus no scale and polish. This study was conducted in general practice and compared both six-monthly and 12-monthly scale and polish treatments with no treatment. This study showed no evidence to claim or refute benefit for scale and polish treatments for the outcomes of gingivitis, calculus and plaque.

https://www.ncbi.nlm.nih.gov/pubmed/24197669

Here’s some related material:

"It turns out that [amyloid-beta proteins] form [plaques] because they're trying to help us. They're trying to fight an infection," said Robert Moir, an assistant professor of neurobiology at Harvard Medical School and the Massachusetts General Hospital.

"The Alzheimer's disease dementia that comes after years of this battle, are something like collateral damage from their actions. But it's not that it's intrinsically bad what they're doing. It's just that if you keep doing it for long enough the amyloid that is generated in this battle starts to become a problem in itself."

If this theory, which Moir outlines in a review article published in the December issue of the journal Alzheimer's & Dementia, proves true, it could mean researchers' current strategies to combat the disease — fighting the plaques — is misguided.

https://www.cbc.ca/radio/quirks/dec-8-2018-why-are-users-tak...

The antimicrobial protection hypothesis of Alzheimer's disease:

https://www.sciencedirect.com/science/article/pii/S155252601...

All the other Alzheimer's researchers are not infectious-disease specialists, and have no reasonable prospect of becoming infectious-disease specialists. The overwhelming majority of Alzheimer's disease research funding still goes to them. They get veto power over most potential grants to infectious-disease groups, and publication by them in most journals.

Probably the single most effective way to enable progress on Alzheimer's research would be to discover something else they could all work on, and stop blocking infectious disease specialists' work.

Amyloid plaque accretion reminds me of cholesterol accretion, and there is a recent school of thought whereby:

- Heart disease is actually caused by metabolic syndrome (read: same cause as diabetes)

- Alzheimers is analogous to diabetes (some are calling it Type 3)

I'm not convinced of the above, but it's interesting.

I found both theories promising.

Your post reminded me of this pub: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709085/

I find the more studies I read, the higher the stakes seem, because the theories I've read are highly contradictory yet their proponents seem very polarized and very sure of themselves. Some theories that have been prematurely accepted by some groups are going to be very, very wrong.

The easiest example of this sort of highly polarized dynamic is in the realm of diets.

> If this theory, which Moir outlines in a review article published in the December issue of the journal Alzheimer's & Dementia, proves true, it could mean researchers' current strategies to combat the disease — fighting the plaques — is misguided.

But it could still mean that preventing the plaque formation would stop the dementia, right?

No, if the plaques are symptoms of a disease, supressing them equals supressing infection symptoms (fever)- you basically feel better but actually prolong the disease and accelerate it somewhat.

>you basically feel better but actually prolong the disease and accelerate it somewhat.

That might be totally fine if the effects of the disease the plaques fight are not as bad as the disease they cause -- e.g. the "prolonged" disease is not as bad as Alzheimer.

But that's worth exploring, right? I'm sure many people would prefer a lucid but shorter life than a longer one that is highly impacted by dementia symptoms

I think the idea is that the plaques are symptoms and that we should invest in the root cause. Like developing antibiotics instead of fever reducers. They both have a role, and I know where I'd allocate my resources.

Afaik, the drugs that reduce plaques have failed to actually alleviate symptoms of the disease.

The emphasis on the plaques comes from the fact that Alzheimer’s is diagnosed by the presence of these plaques, while dementia is a symptom/presentation.

I guess it comes down to whether you believe that an infection disproportionately affects old people and causes dementia. It probably doesn’t, not for any good biological reason, but because it doesn’t sound like any progress has been made on the biomechanics of dementia.

Laypeople obviously don’t care about the plaques. They want the dementia to go away. You can make a mouse model that has a brain infection, and then potentially a model where that infection shows plaques, and then a molecule that gets rid of the infection. But it’s really hard to tell (in real life, not in science speak) if a mouse has dementia. That’s the limitation.

We’re so incredibly far away from drug interventions for dementia.

> I guess it comes down to whether you believe that an infection disproportionately affects old people and causes dementia.

What they're saying is that after many years of fighting the infection Alzheimer's starts to develop. Certainly people who are older have the potential to have more years of infection. This seems plausible.

>I guess it comes down to whether you believe that an infection disproportionately affects old people and causes dementia. It probably doesn’t, not for any good biological reason

How about older people not having the health required to fight the infection?

There is a clinical trial associated with the anti-gingipain treatment described in OPs study that is going into phase 2 this month. If the authors are correct, people are going to be getting this treatment for alzheimers this year.

given the catastrophic failure of every single plaque therapy ever tried over the last 30 years, i’m going with “certainly misguided”.

Money quote:

"The Kgp inhibitor COR271, which has oral bioavailability and significant CNS penetration, administered orally twice a day significantly reduced bacterial load in the brain compared to the positive control infection arm and in comparison to baseline levels at 5 weeks."

Any idea of cost for future therapeutic doses?

And yet the risk increase for dementia for people with periodontitis is not large at 6% in a recent sizable study.

https://www.healthinaging.org/blog/periodontitis-may-raise-t...

Good data point. However, this suggests that the barriers between oral infection -> vascular infection -> brain infection are somewhat effective.

This may also help explain why neurosurgeons who operate on Alzheimer's patients are more likely to develop Alzheimer's themselves:

https://alzgerm.org/news/reports-indicate-brain-surgeons-ris...

https://www.ncbi.nlm.nih.gov/pubmed/20170305

So... my memory has gotten a LOT worse in the last few years. I've started making more spelling mistakes, and just thinking less clearly in general. There is alzheimers disease in my ancestry as well, and I'm worried I'm on track for dementia, even just as a 30-something. It happens to correlate pretty well to the time since I stopped using Listerine regularly, FWIW.

I see things about fighting alzheimers with vigorous exercise, consumption of mushrooms, etc. From this I would think that using Listerine would be beneficial for eliminating a potential source of P. gingivalis infection.

Anybody else facing this predicament? What is your approach?

As others have said, talk to your doctor, but I'll add this incentive: While there are no cures for Alzheimer's, there are things that have a good chance of slowing it down, some of which may be available only via prescription.

I'm familiar with the "not sure I really want to know" kind of thing myself, but there are outcomes that can be more positive than just letting it happen. If it is Alzheimer's, you want to get started as soon as possible.

I'll also point out there are plenty of non-Alzheimer's explanations, some of which may be as simple as a missing nutrient or a relatively-easily-treatable thyroid condition. Or maybe you've got sleep apnea without realizing it. Or who knows how many other things. I obviously can't guarantee you aren't experiencing Alzheimer's in some form, but there's a lot of other things on the table too.

Why not try using listerine again? you could do some spelling tests to try and benchmark yourself.

Discovering that listerine improves spelling would be definitely something :) Hey, if you publish serious research on it, whatever the outcome, you're in for an IgNobel, no doubt.

Invest in a carbon monoxide detector, also you might want to make sure you're eating a healthy diet, don't have any nutrient deficiencies or imbalances, and get enough sleep and exercise.

Shouldn't you get an examination and doctor advice (or at least look for an approach based on the results) as opposed to random old wives tales from us HN users?

Why wouldn't you try using listerine?

By all means talk to your doctor about fog/memory issues but reducing oral bacteria isn't an old wives tale and is standard dentist advice either through brushing / listerine or other methods.

You're focusing on the wrong thing. The parent believes they might have Alzheimer.

Without getting diagnosed, and without starting treatment if indeed have it, mere questions about using Listerine should be at the very bottom of their list, as should be HN advice.

From the Discussion section of TFA: “In addition, there is one other species of Porphyromonas that is known to produce gingipains, Porphyromonas gulae (61). P. gulae is a natural inhabitant of the oral cavity of companion animals such as dogs, and a recent study demonstrated that dogs can transmit P. gulae to the oral cavity of their owners (62). Research is underway to determine whether P. gulae may be contributing to the gingipain load in AD brains.”

Since 1999 there have been reports of Herpes-family viral infections associated with Alzheimer's, with publication only recently enabled. What is up with that work?

Not sure I understand your question.

1. New results? Check Medline!

2. What the problem is? I vaguely remember that this might have been on hackernews recently: https://www.statnews.com/2018/10/29/alzheimers-research-outs...

For an overarching theory, see the book: Microbial Burden: A Major Cause Of Aging And Age-Related Disease by by Michael Lustgarten.

Also related: What if we found out that blood microbiome is the most significant marker of heart disease? E.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328378/

I recall reading Slackware's Patrick Volkerding's health problems were traced back to his sonic toothbrush. [1]

tl;dr The sonic toothbrush was aerosolizing the bacteria in his mouth which was inhaled while brushing his teeth.

[1] - https://science.slashdot.org/story/04/11/16/1846207/patrick-...

Archived copy of the original article:

https://web.archive.org/web/20041118015127if_/http://slackwa...

Sounds like what Dale Bredesen is saying.

https://www.foundmyfitness.com/episodes/dale-bredesen

How does this compound with the Taiwanese study on relation between herpes viruses and Alzheimer?

Ergo, floss.

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