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- Helicobacter pylori -


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Helicobacter pylori (the stomach ulcer bacteria):


See also  Infection and Immune System Response
          Broccoli Sprouts
          Cinnamon
          Enbrel
          Methylene blue
          Rember

Can a Helicobacter pylori bacterial infection be the root cause of many (75%) cases of Alzheimer's disease cases?  Genetic or other factors would then comprise the root cause of the other 25%.

"Eradication of Helicobacter pylori may be beneficial in the management of Alzheimer’s disease"
Abstract: Infectious agents have been proposed as potential causes of Alzheimer’s disease (AD). Recently, we documented a high prevalence of Helicobacter pylori (Hp) infection in patients with AD. We aim to access the effect of Hp eradication on the AD cognitive (MMSE: Mini Mental State Examination and CAMCOG: Cambridge Cognitive Examination for the Elderly) and functional (FRSSD: Functional Rating Scale for Symptoms of Dementia) status parameters. In the first part of the study, a total of 50 consecutive patients with AD and 30 age-matched anaemic controls underwent an upper gastrointestinal endoscopy, and gastric mucosal biopsies were obtained to detect the presence of Hp infection by histologic analysis and rapid urease test. Serum anti-Hp-specific IgG level was analysed by enzyme-linked immunosorbent assay. In the second part, Hp-positive AD patients received a triple eradication regimen (omeprazole, clarithromycin and amoxicillin), and all patients were followed up for 2 years, while under the same treatment with cholinesterase inhibitors. Hp was detected in 88% of AD patients and in 46.7% of controls (P < 0.001). Hp eradication was successful in 84.8% of treated patients. At the 2-year clinical endpoint, cognitive and functional status parameters improved in the subgroup of patients where Hp eradication was successful (P < 0.001 and P = 0.049 for MMSE and CAMCOG, respectively; P < 0.001 for FRSSD), but not in the other patients. Hp eradication may positively influence AD manifestations, suggesting a possible common link between Hp and AD.
http://www.springerlink.com/content/83147756538x7031/?p=4d07d65b60894df3bab4620921dcd1e6&pi=2

What caught my attention is this statement: "At the 2-year clinical endpoint, cognitive and functional status parameters improved in the subgroup of patients where Hp eradication was successful ..., but not in the other patients. Hp eradication may positively influence AD manifestations, suggesting a possible common link between Hp and AD."

I have to connect the links here to AD here.

We've recently read that corrupted tau proteins can have characteristics similar to the prions of "mad cow disease", scrapie, chronic wasting disease of deer, and CJD of humans:

Rogue protein 'spreads in brain'
BBC Sunday, 7 June 2009
Scientists have shown a rogue protein thought to cause Alzheimer's can spread through the brain, turning healthy tissue bad. They believe the tau protein may share characteristics with the prion proteins which cause vCJD. When injected into the brains of healthy mice it triggered formation of protein tangles linked to Alzheimer's. However, experts stressed the Nature Cell Biology study did not mean tau could be passed from person to person. Tau is a protein present in all nerve cells, where it plays a key role in keeping them functioning properly. But a rogue form of the protein can trigger the formation of protein clumps within nerve cells known as neurofibrillary tangles. It is thought that these tangles are likely to be a major cause of Alzheimer's disease... Tau is a protein present in all nerve cells, where it plays a key role in keeping them functioning properly. But a rogue form of the protein can trigger the formation of protein clumps within nerve cells known as neurofibrillary tangles. It is thought that these tangles are likely to be a major cause of Alzheimer's disease.
http://news.bbc.co.uk/2/hi/health/8084787.stm

It is interesting to note that the degeneration tends to follow the path of neural networks:

Neuronal subpopulations and genetic background in tauopathies: a catch 22 story?
L. Bue´e*, A. Delacourte
Neurobiology of Aging 22 (2001) 115–118
"...these vulnerable neurons degenerate following precise pathways. Regarding encephalopathy such as PEP, it is clear that a virus follows neural networks for its propagation. It is now well established that there is also a sequential degeneration of vulnerable networks of neurons in AD and PSP. In AD, both biochemical and neuropathological studies show that NFT formation starts in the hippocampal formation (from transentorhinal to entorhinal and then hippocampus), progresses sequentially as follows anterior, inferior and medium temporal cortex, and then spreads into polymodal association areas, unimodal areas and primary and/or sensory areas..."
http://www.alzheimer-adna.com/pdf/2001/2001Bueecatch22.pdf

Path Is Found for the Spread of Alzheimer’s
By GINA KOLATA February 1, 2012

Alzheimer’s disease seems to spread like an infection from brain cell to brain cell, two new studies in mice have found. But instead of viruses or bacteria, what is being spread is a distorted protein known as tau...
http://www.nytimes.com/2012/02/02/health/research/alzheimers-spreads-like-a-virus-in-the-brain-studies-find.html

Alzheimer's Disease May Spread by 'Jumping' from One Brain Region to Another
ScienceDaily (Feb. 1, 2012) — For decades, researchers have debated whether Alzheimer's disease starts independently in vulnerable brain regions at different times, or if it begins in one region and then spreads to neuroanatomically connected areas. A new study by Columbia University Medical Center (CUMC) researchers strongly supports the latter, demonstrating that abnormal tau protein, a key feature of the neurofibrillary tangles seen in the brains of those with Alzheimer's, propagates along linked brain circuits, "jumping" from neuron to neuron...
http://www.sciencedaily.com/releases/2012/02/120201173217.htm

Trans-Synaptic Spread of Tau Pathology In Vivo.
Li Liu, Valerie Drouet, Jessica W. Wu, Menno P. Witter, Scott A. Small, Catherine Clelland, Karen Duff. PLoS ONE, 2012; 7 (2): e31302 DOI: 10.1371/journal.pone.0031302
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0031302

Vulnerable Brain Region May Be Central to Progression of Alzheimer's Disease
ScienceDaily (Nov. 7, 2010)
New research is helping to unravel the events that underlie the "spread" of Alzheimer's disease (AD) throughout the brain. The research, published by Cell Press in the November 4th issue of the journal Neuron, follows disease progression from a vulnerable brain region that is affected early in the disease to interconnected brain regions that are affected in later stages... "Our findings directly support the hypothesis that AD-related dysfunction is propagated through networks of neurons, with the EC as an important hub region of early vulnerability,"...
http://www.sciencedaily.com/releases/2010/11/101103135239.htm

[Note:  here seems to be a similar progression in Parkinson's disease: 

How The Pathology Of Parkinson's Disease Spreads
ScienceDaily (July 29, 2009) — Accumulation of the synaptic protein alpha-synuclein, resulting in the formation of aggregates called Lewy bodies in the brain, is a hallmark of Parkinson's and other related neurodegenerative diseases. This pathology appears to spread throughout the brain as the disease progresses. Now, researchers at the University of California, San Diego School of Medicine and Konkuk University in Seoul, South Korea, have described how this mechanism works... "The discovery of cell-to-cell transmission of this protein may explain how alpha-synuclein aggregates can pass to new, healthy cells," said first author Paula Desplats, project scientist in UC San Diego's Department of Neurosciences. "We demonstrated how alpha-synuclein is taken up by neighboring cells, including grafted neuronal precursor cells, a mechanism that may cause Lewy bodies to spread to different brain structures."... In these studies, autopsies of deceased Parkinson's patients who had received implants of therapeutic fetal neurons 11 to 16 years prior revealed that alpha-synuclein had propagated to the transplanted neurons...
http://www.sciencedaily.com/releases/2009/07/090727191914.htm

How Disordered Proteins Spread from Cell to Cell, Potentially Spreading Disease

ScienceDaily (Feb. 18, 2011) — ...Kopito found that the mutant protein associated with Huntington's disease can leave one cell and enter another one, stirring up trouble in each new cell as it progresses down the line. The spread of the misfolded protein may explain how Huntington's progresses through the brain.

This disease, like Parkinson's and Alzheimer's, starts in one area of the brain and spreads to the rest of it. This is also similar to the spread of prions, the self-replicating proteins implicated in mad cow disease and, in humans, Creutzfeldt-Jakob disease. As the misfolded protein reaches more parts of the brain, it could be responsible for the progressive worsening of these diseases...
http://www.sciencedaily.com/releases/2011/02/110218165254.htm
]

Apparently, the amyloid beta plaques have prion-like properties too:

Alzheimer's has 'infectious' mechanism
Cosmos Online
Monday, 25 October 2010

by Gareth Barton

These misfolded proteins have properties similar to prions, the researchers concluded. Prions are tiny, infectious protein particles can cause disease, such as mad cow disease which passes from infected cattle to humans through their meat.


In the study, the researchers removed brain tissue from mice with Alzheimer's-like symptoms, and injected into it into the stomach cavity of healthy mice. Four months later, the previously healthy mice showed symptoms similar to those of Alzheimer's disease and their brains had similarly disease brain tissue.
http://www.cosmosmagazine.com/news/3824/alzheimers-disease-has-infectious-element


Peripheral Induction of Alzheimer's-Like Brain Pathology in Mice
ScienceDaily (Oct. 25, 2010)
Pathological protein deposits linked to Alzheimer's disease and cerebral amyloid angiopathy can be triggered not only by the administration of pathogenic misfolded protein fragments directly into the brain but also by peripheral administration outside the brain...
http://www.sciencedaily.com/releases/2010/10/101021141453.htm


Peripherally Applied Aβ-Containing Inoculates Induce Cerebral β-Amyloidosis
Yvonne S. Eisele
Science DOI: 10.1126/science.1194516
Published Online October 21, 2010
The intracerebral injection of β-amyloid–containing brain extracts can induce cerebral β-amyloidosis and associated pathologies in susceptible hosts. Here, we found that intraperitoneal inoculation with β-amyloid–rich extracts induced β-amyloidosis in the brains of β-amyloid precursor protein transgenic mice after prolonged incubation times
http://www.sciencemag.org/cgi/content/abstract/science.1194516

Could A-beta plaques from animal tissue in our food be a problem?  I'm not a vegetarian, but (pardon the pun) it is food for thought.

Can toxins produced by bacteria initiate the process?

Profiling the culprit in Alzheimer's disease (AD): bacterial toxic proteins - Will they be significant for the aetio-pathogenesis of AD and the transmissible spongiform encephalopathies?
Schmitt HP. Institute of Pathology, Department for Neuropathology, University of Heidelberg, Germany
http://www.ncbi.nlm.nih.gov/pubmed/17337124?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Can a Hp infection explain the success some people have been experiencing with the "perispinal Enbrel injections"? Enbrel is thought to work by inhibiting the effects of "tumor necrosis factor alpha", (TNF-alpha). And guess what substance a Helicobactor pylori infection in the stomach causes the body to produce? Yep, TNF-alpha. In the full text of the Heliobacter article, it says on page 8, "However, Hp, an extracellular bacterium, could affect the brain and other target organs, such as the heart, indirectly, through the release of numerous cytokines, including TNF-[alpha] acting at a distance."

To me, this gives a reason for why the perispinal injection of Enbrel should work, why reports of its success are not merely wishful thinking. It's the link to a cause that validates the idea. I think that the success of Enbrel also supports the theory for the mechanism by which Hp in the stomach affects the brain.

For those experiencing improvements from Enbrel treatments, I think this says, check to see if there is also an H-pylori infection present. If so, treating the H.pylori infection may increase the time needed between treatments, or may even eliminate the need for Enbrel treatments entirely.  (There may be other bacteria or viruses that could cause the body to produce TNF-alpha, such as Herpes simplex virus type 1 (HSV1) and Chlamydophila (Chlamydia) pneumoniae.)

Here is the link to the full text of the paper. Even for those like me, still in the process of learning language of biochemistry, it is understandable enough for one to grasp the ideas.  (It is rarely necessary to know the intimate details of how a computer works in order to be effective in using a computer.):
http://www.springerlink.com/content/83147756538x7031/fulltext.pdf

Wild speculation time:
If an Hp infection turns out to be the initiating factor
in many cases of AD, then for those currently suffering with the disease, I would first stop the progression, then eradicate the infection(s). We appear to have at least two ways to stop the progression at this time: Enbrel or the MCT oil regimen. They don't seem to conflict, targetting different steps of the disease process, so it would probably be wise to use both.  There may also be some benefit to suing the tau busters, as this may attack even another step in the disease process.

Obviously, if eliminating a chronic bacterial infection reduces the body's production of TNF-alpha to normal levels, there would be no need for TNF-alpha blocking drugs such as Enbrel. This news will not be greeted with enthusiasm by the pro-Tobinick faction.  Nor will it make the "there's nothing we can do, we're powerless, everyone should just die now and get it over with" crowd happy.

In the Greek study, Hp was detected in 88% of AD patients. Hp eradication was successful in 84.8% of treated patients, which is about normal for all cases of Hp infection.  If you multiply 88% by 84.8%, you get ~75%... which, coincidently, seems to be about the percentage of people that are helped by MCT/coconut oil.

I'm sure people are thinking, my loved one never had a stomach ulcer, yet now she has AD.  Well, one does not need to have an ulcer to have an Hp infection. I don' t know where they got this statistic, but I found...

"In countries with poor sanitation, 90% of the adult population can be infected. In the U.S., 30% of the adult population is infected."
http://www.medterms.com/script/main/art.asp?articlekey=3676

90% of the people with an Helicobacter pylori (Hp) infection do not have stomach trouble or ulcers. Or, to put it another way, only 10% of people with an Hp infection have stomach trouble.

"H. pylori gastritis produces no symptoms in 90 percent of infected persons. The prevalence of H. pylori infection varies geographically and has been demonstrated to be as high as 52 percent in the United States. Factors associated with higher infection rates are increasing age, African-American or Hispanic race, lower levels of education, and birth in a developing country."
http://www.aafp.org/afp/20020401/1327.html

I'm sure that not everyone with an Hp infection will develop AD. However, one of the greatest risk factors for developing AD is age.  Perhaps the cumulative effects of a chronic H.pylori infection explains this.

I looked up the statistics for Aricept. It is only effective for 50% of the people who take it, and then, it is only effective for about 6 to 12 months.

If the statistics of the Greek study holds true, then one could expect the eradication of an Hp infection to be effective for about 75% of those treated, and that the effect should last at least 2 years (which was the limit of how long they tracked the test participants).

If I were in charge of an insurance company, I think I would consider the cost of treating an Hp infection followed by the stabilization of the patient as a discount when compared to six months worth of Aricept, followed by the cost of a nursing home.

There are some interesting charts in the full text .pdf file of the paper:
http://www.springerlink.com/content/83147756538x7031/fulltext.pdf


The original article was from researchers in Greece, so the statistics given for the prevalence of Hp infection may be different in your country.

Another thought I had was that the treatment for Hp is a two or three week course of multiple antibiotics. This probably knocks out a whole bunch of other bacteria in all parts of the body. What if the culprit is NOT Hp, but gets killed off by the Hp antibiotics?

Whatever the case, I think there are some simple tests such as a blood test for Hp antibodies, or this "breath test" that could be done relatively easily. I think it's worth asking the phsyicians about.

From what I've read, this bug is particularly hard to treat. They seem to be using a cocktail of three drugs for something like 14 days. The antibiotics can have side effects, making the treatment unpleasant.


I started thinking, what substances, other than prescription antibiotics, inhibit or eliminate Hp bacteria? I've heard that Pepto-Bismol will (the bismuth in it). And then I remembered that in Chinese medicine, cinnamon had long been used to treat stomach problems. A quick search of the Internet found that yes, indeed, cinnamon has been and is being investigated for its anti-Hp potential. But, which component of cinnamon is it? I don't know. This may mean that using whole ground cinnamon may be more effective than using extracts.

Some foods or spices may also reduce the Hp infection, but I haven't found anything yet, other than prescription antibiotics, that will eliminate it.  Broccoli sprouts, dill, and cinnamon may be good candidates.  "Probiotics", or "good bacteria" may help by crowding out the H-pylori.  Others will have to be explored.

For broccoli sprouts, it's the sulforaphane in them that seems to help.

Of course, if you can get a physician to test for Hp, and then prescribe antibiotics, go for it!

There are probably several conditions that eventually lead to AD. This particular one would not address genetic causes or exposure to a toxin.

I doubt that this is the end of the story. Never the less, I think that the idea of Helicobacter pylori being involved should be aggresively researched.
If eliminating a Helicobacter pylori infection worked for 3 out of 4 cases, that would be a good start!  How much needless suffering could be avoided if people only knew this?

I started thinking about other antibiotics. I read that methylene blue is used as an antibiotic to treat urinary tract infections, malaria, and even bacteria "infections" in fish aquariums. Does it also eliminate Hp? Could that be why it has helped people with AD (Rember study)? Well, maybe. I found this article, but I don't have the whole text. It is intriguing.

"Evaluation of methylene blue and triple therapy for eradication of Helicobacter pylori infection in the nude mouse model"
KARITA M. (1) ; TADA M. (1) ; OKITA K. (1) ; TSUDA M. ; NAKAZAWA T.
International symposium on Helicobacter pylori and its diseases No5, Tokyo , JAPON (04/04/1992)
1993, vol. 5, SUP1 (6 ref.), pp. S79-S83
European journal of gastroenterology & hepatology

Abstract: "Objective: To determine how far Helicobacter pylori infection can be eradicated with methylene blue and triple therapy (amoxicillin, metronidazole, bismuth subnitrate), using a nude mouse model. Methods: Four weeks after inoculation of H. pylori into the stomach, two groups of nude mice were administered methylene blue or triple therapy via the stomach for 1 week. A control group of nude mice was given culture fluid alone after the inoculation. The number of H. pylori and histological changes in the stomach were determined weekly for 5 weeks, starting from the completion of drug administration. Results: In the methylene blue treatment group, the concentration of H. pylori was significantly reduced for 1-3 weeks after treatment compared with the control group..."
http://cat.inist.fr/?aModele=afficheN&cpsidt=4893514

It is interesting to note in this article about the experimental drug Rember,
ICAD: Tau-Targeted Therapy Slows Alzheimer's Progression for 19 Months it says,

"In the trial reported here, 321 patients were randomized to 30 mg, 50 mg, 100 mg or placebo. The drug, Dr. Wischik said, was effective when it dissolved in the stomach, but was not effective when the drug was absorbed through the intestines. This was an issue for the 100-mg dose, which had 'absolutely no activity because it didn't dissolve in the stomach.'"
http://www.medpagetoday.com/MeetingCoverage/ICAD/10320

As I wrote above, the Helicobacter pylori bacteria finds methylene blue to be rather toxic. This tends to support the idea that the dominant effect of Rember may not have been as a "Tau aggregation inhibitor (TAI)", but rather as an antibiotic. This would explain why the 100mg dose was not effective when it dissolved in the intestines, whereas the 30 and 60mg doses, which disolved in the stomach, were effective. The antibiotic effect of the rember (which is basically methylene blue) reduced the H.pylori infection, thereby reducing the TNF levels. It seems to me that anyone getting Enbrel injections to reduce TNF levels should take a hard look at this.

A final thought on this topic, this concept may also apply to the other rare neurodegenerative diseases such as PSP, CBD, the FTD, etc.

Other things to research:  Lauric acid in coconut oil kills H.pylori?

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Updated: July 2, 2012
Inception: July 2, 2012