We may know what causes Alzheimer’s-and how to stop it

[tcphillips]

We may finally know what causes Alzheimer’s – and how to stop it

A. DOWSETT, PUBLIC HEALTH ENGLAND/SCIENCE PHOTO LIBRARY

By Debora MacKenzie

If you bled when you brushed your teeth this morning, you might want to get that seen to. We may finally have found the long-elusive cause of Alzheimer’s disease: Porphyromonas gingivalis, the key bacteria in chronic gum disease.

That’s bad, as gum disease affects around a third of all people. But the good news is that a drug that blocks the main toxins of P. gingivalis is entering major clinical trials this year, and research published today shows it might stop and even reverse Alzheimer’s. There could even be a vaccine.

Alzheimer’s is one of the biggest mysteries in medicine. As populations have aged, dementia has skyrocketed to become the fifth biggest cause of death worldwide. Alzheimer’s constitutes some 70 per cent of these cases and yet, we don’t know what causes it.

Bacteria in the brain

The disease often involves the accumulation of proteins called amyloid and tau in the brain, and the leading hypothesis has been that the disease arises from defective control of these two proteins.

But research in recent years has revealed that people can have amyloid plaques without having dementia. So many efforts to treat Alzheimer’s by moderating these proteins have failed that the hypothesis has been seriously questioned.
Read more: Here’s how to avoid gum disease

However evidence has been growing that the function of amyloid proteins may be as a defence against bacteria, leading to a spate of recent studies looking at bacteria in Alzheimer’s, particularly those that cause gum disease, which is known to be a major risk factor for the condition.

Bacteria involved in gum disease and other illnesses have been found after death in the brains of people who had Alzheimer’s, but until now, it hasn’t been clear whether these bacteria caused the disease or simply got in via brain damage caused by the condition.
Gum disease link

Multiple research teams have been investigating P. gingivalis, and have so far found that it invades and inflames brain regions affected by Alzheimer’s; that gum infections can worsen symptoms in mice genetically engineered to have Alzheimer’s; and that it can cause Alzheimer’s-like brain inflammation, neural damage, and amyloid plaques in healthy mice.

“When science converges from multiple independent laboratories like this, it is very compelling,” says Casey Lynch of Cortexyme, a pharmaceutical firm in San Francisco, California.

In the new study, Cortexyme have now reported finding the toxic enzymes – called gingipains – that P. gingivalis uses to feed on human tissue in 96 per cent of the 54 Alzheimer’s brain samples they looked at, and found the bacteria themselves in all three Alzheimer’s brains whose DNA they examined.

“This is the first report showing P. gingivalis DNA in human brains, and the associated gingipains, co-lococalising with plaques,” says Sim Singhrao, of the University of Central Lancashire, UK. Her team previously found that P. gingivalis actively invades the brains of mice with gum infections. She adds that the new study is also the first to show that gingipains slice up tau protein in ways that could allow it to kill neurons, causing dementia.

The bacteria and its enzymes were found at higher levels in those who had experienced worse cognitive decline, and had more amyloid and tau accumulations. The team also found the bacteria in the spinal fluid of living people with Alzheimer’s, suggesting that this technique may provide a long-sought after method of diagnosing the disease.

When the team gave P. gingivalis gum disease to mice, it led to brain infection, amyloid production, tangles of tau protein, and neural damage in the regions and nerves normally affected by Alzheimer’s.

Cortexyme had previously developed molecules that block gingipains. Giving some of these to mice reduced their infections, halted amyloid production, lowered brain inflammation and even rescued damaged neurons.

The team found that an antibiotic that killed P. gingivalis did this too, but less effectively, and the bacteria rapidly developed resistance. They did not resist the gingipain blockers. “This provides hope of treating or preventing Alzheimer’s disease one day,” says Singhrao.
New treatment hope

Some brain samples from people without Alzheimer’s also had P. gingivalis and protein accumulations, but at lower levels. We already know that amyloid and tau can accumulate in the brain for 10 to 20 years before Alzheimer’s symptoms begin. This, say the researchers, shows P. gingivalis could be a cause of Alzheimer’s, but it is not a result.

Gum disease is far more common than Alzheimer’s. But “Alzheimer’s strikes people who accumulate gingipains and damage in the brain fast enough to develop symptoms during their lifetimes,” she says. “We believe this is a universal hypothesis of pathogenesis.”

Cortexyme reported in October that the best of their gingipain blockers had passed initial safety tests in people, and entered the brain. It also seemed to improve participants with Alzheimer’s. Later this year the firm will launch a larger trial of the drug, looking for P. gingivalis in spinal fluid, and cognitive improvements, before and after.

They also plan to test it against gum disease itself. Efforts to fight that have led a team in Melbourne to develop a vaccine for P. gingivalis that started tests in 2018. A vaccine for gum disease would be welcome – but if it also stops Alzheimer’s the impact could be enormous.

Journal reference: Science Advances

[ProDigit]

So what would you suggest us do for recovery, if we don't want to pay for overpriced drugs? Chew on mint leaves?

[Nert]

Cortexyme reported in October that the best of their gingipain blockers had passed initial safety tests in people, and entered the brain. It also seemed to improve participants with Alzheimer’s. Later this year the firm will launch a larger trial of the drug, looking for P. gingivalis in spinal fluid, and cognitive improvements, before and after.

Interesting article. Seems to provide more evidence that amyloid plaques are the result some other process rather than a cause for the disease. Good to see some different approaches being used, and some possible new treatments for this horrible disease.

Thanks

[Ricorocks]

I wish them luck & hope they find & cure! Often times it just does not work out, one should not get to excited at this stage.

https://www.azcentral.com/story/news/he ... 675823002/

[bruce]

In the meantime, we already know that general lifestyle characteristics show a correlation. (Heath healthy, get plenty of exercise, don't smoke, don't get old, etc. which MIGHT reduce your chances of getting it.) We can add "brush your teeth" to the list even though it might not help, it can't hurt.

[Nert]

I just came across an article that I really liked. It describes a possible cause and treatment for various neuro-degnerative. The theory is that a toxin (BMAA) associated with cyanobacteria causes damage to the brain. The belief is that BMAA insinuates "... itself into protein chains in place of one of the 20 standard amino acids, causing misfolding that can trigger the death of neurons." The amino acid L-serine is identified as the BMAA target. The article describes the effects of BMAA in animal tests that are similar to those associated with Alzheimer's and other neuro-degenerative diseases. It also cites some clusters of these types of diseases in areas with high concentrations of BMAA in the environment. "Despite such findings, the ... work is far from accepted science." A stage 2 trial to evaluate the effects of L-serine supplements in slowing progression of Alzheimer's and ALS is ongoing at Dartmouth.

The following link has a video and a longish article. The video is kind of a synopsis. The article contains more detailed information. I thought the article was very well written and worth the time spent reading it. The last part describing dietary characteristics of residents of Ogimi in Japan was particularly fascinating. "Ogimi advertises itself as the Village of Longevity; it has the most centenarians per capita, according to the World Health Organization."

Here's the link to the article.

http://fortune.com/longform/alzheimers- ... akthrough/

[Vester]

Deleted. Wrong topic.

[Ricorocks]

Seems like a great playground for Alzheimer's research would be, some small country (can't recall the name), where almost all get by age 40. Nevermind if that's aready a research playground.

@Bruce I think you hit the nailed it!

snip "So it's actually the altered microbiota that are causing the bone loss, not P. gingivalis itself, which remains at low concentrations," Dr. Hajishengallis said.

A healthy mouth just might ward off disease, which would be the things Bruce mentioned, which would not shift the mouths microbiota, to cause danger, to the host. Some interesting approaches (near end of article) lozenges, tooth paste, mouth wash. May be coming soon.


https://www.drbicuspid.com/index.aspx?s ... mid=309686

[Ricorocks]

dementia seems to be a precursor of Alzheimer's, perhaps prolonging dementia, also (may) prolong Alz... More on Bruce's healthy living.

https://i.postimg.cc/NFXVPPFk/2019-01-28-11-41-03.png if too small print maybe

https://postimg.cc/rR8QDjSD this makes the print giant size, when clicked

https://www.nytimes.com/2019/01/28/heal ... rment.html direct link, when tested using FF said broken link, but worked in chrome

[Ricorocks]

Over the years serving size has increased, so has obesity, seems Alzheimrs's has a direct link to, what we eat & how much, not a stretch to believe poor life style, can disrupt, mouth microbiota, and may add, brain disease.

https://www.nytimes.com/2019/01/28/well ... ntrol.html

Today my wife & myself are going to "Lupes Tortilla" for dinner, one order & we will share. If she's ok with that.

[Ricorocks]

Two approaches in this thread: 1. We treat symptoms 2. To avoid those symptoms, live a healthy life. The food industry seems to be in 'collusion' with the drug industry.

From the SF Examiner, I liked:

"During the Super Bowl telecast, there will be no commercials for medicinal marijuana. That ad was rejected by the network, which wants to protect America from the evils of weed. There will be dozens of commercials for booze, bacon cheeseburgers, junk snacks, toxic colas, candy, large automobiles that hasten global warming, and wonder drugs designed to treat the ailments cause by all the other stuff being advertised. The wheel of life."

[Ricorocks]

“We have the edges of the puzzle, and we’re now trying to figure out what’s in the picture itself,” she said."

https://www.nytimes.com/2019/01/28/heal ... entia.html

probiotics, for mouth & body look interesting, that Dr. Bicuspid article, towards the end of article mentions lozenges, toothpaste, mouth wash, rights the microbiome, that MAY help or delay Alz.

To do that may or may not cause harm as the jury is still out

[bruce]

dementia seems to be a precursor of Alzheimer's, perhaps prolonging dementia, also (may) prolong Alz...

In scientific terms, Alzheimer's is one form of a more general class of diseases called dementia, and the latter is a behavioral diagnosis, not a cellular diagnosis. (It used to be said that Alz can only be diagnosed by autopsy. I don't know if that's still the case.)


In common parlance, the words are often used interchangeably.

[Ricorocks]

@Bruce Okay! Before full blown onset of Alz, dementia, can & does occur, a leading factor, in dementia is BP. I believe I've posted an NY Times article on BP/Dementia, study reported by Jama. Perhaps early dementia, is actually the start of Alz, but we see tao proteins, indicating CTE, posthumously. Pretty much said what you said here. Alz & CTE share many similarities, CTE is close to diagnostics, on the living.

Alz is not just one bad guy, more than one factor is involved: genetics, BP, eating habits, dental health, concussion. all are Known contributing factors, or strongly suspected.

Just targeting one factor, may still allow Dementia/Alz to occur.

That's why your comment (NEAR TOP OF THIS THREAD), is so important: Exercise, eat right yada yada is so important, by doing so you eliminate, some known factors which can lead to Dementia/Alz.

The BP article, is not scientific proof, that elevated BP causes Dementia/Alz, but it's closely related. Theory not proof!

[Ricorocks]

https://www.nytimes.com/2019/03/01/heal ... ments.html