www.perpetualcommotion.com
"Give with a free hand, but give only your own."
 -- J.R.R. Tolkien The Children of Hurin
- The Role of Infection and Inflammation in Neurodegenerative Diseases -


Brain Inflammation
Cat's Claw
Chitosan
Green Tea
Helicobacter pylori

 Herpes Simplex Virus
Immune System Reponse
 Lyme Disease
 Neurospirochetosis
.

 		Tetracyclines
TNF Alpha
.
 

Here’s a wild idea.  Epidemiological studies in India have found that the incidence of AD in that country are quite low [Reference].  We have been thinking that this is due to the curcumin content of curry powder (via turmeric) used in Indian cooking.  However, most of us have been assuming that the objective is to get the curcumin into the blood.  Maybe this shouldn’t be our only objective.  Turmeric has been used for millennia as a food preservative.  Therefore, it is reasonable to assume that it has some bactericidal properties.  Could it be that exposing the spirochete bacteria in the mouth to turmeric kills off a strain that causes AD?  The same goes for green tea.  The incidence of dementia for those who consume green tea regularly is lower. [Reference].  Naturally, I thought that that throwing a few green tea extract supplements into the daily supplement regimen would do the trick.  But again, maybe it is the exposure of harmful bacteria to the tea in the mouth that is responsible for its effectiveness.  Green tea appears to also have bactericidal properties [Reference].  The same could be said for whole cinnamon, red wine, and who knows what else.  I’m sure that pharmaceuticals or chemicals such as lowly old baking soda may be even more effective.  Somewhere I read someone speculating about the “life cycle” of these spirochetes.  Do they multiply only in the mouth and travel to the brain (and other organs), or do they multiply in the other organs once they get there?  The latter seems more likely, but if the former is true, then there seems to be good reason to aggressively pursue ways to killing them off in the mouth.

Spirochetes, at least the Treponema varieties I’ve read about so far, are “anaerobic”:  They don’t do well in oxygen.  This might explain why exercising and activity is linked to reduced or at least delayed dementia.  It may also be why sleep apnea sometimes leads to cognitive impairment.

The spirochete Borellia burgdorferi that causes Lyme disease appears to be incredibly difficult to eradicate.  It may not be possible to rid the body of the periodontal spirochetes either.

********************************************************************************************
Brain Inflammation The Role of Brain Inflammation in Neurodegenerative Diseases

See also AFA, ALA, Anatabine, Blueberries, Cat's Claw, CCSVI, Chitosan, Cinnamon, Curcumin,
         Enbrel (Etanercept), Herpes simplex virus (HSV-1), Infection and Immune System Response,
         Leukine, NSAIDs, Nypta, TNF-Alpha,  

There are so many references in my notes to the suspected role of brain inflammation in neurodegenerative diseases that I thought that a section dedicated to this topic was warrented.

Potential Alzheimer's Treatment? Newly Discovered Role for Enzyme in Neurodegenerative Diseases

ScienceDaily (Mar. 11, 2011) — Neurodegenerative diseases like Alzheimer's and Parkinson's are partly attributable to brain inflammation... "The caspases are a group of enzymes known for causing cell death," says Associate Professor Bertrand Joseph, who headed the study. "That they also serve as signal molecules that govern that activity of other cells was an unexpected discovery that gives them an entirely new physiological role."...
http://www.sciencedaily.com/releases/2011/03/110310070449.htm


********************************************************************************************
Neurospirochetosis (Spirochetes)

Wikipedia entry for spirochetes

http://en.wikipedia.org/wiki/Spirochetes


I don't even know where to begin with this one. I first read the abstract, and thought, hmmm... this is interesting. Then I waded through the "provisional full text .pdf". The author links together so many clues to this mystery that she has me me thinking, *this* might be the cause to not only Alzheimer's disease and its relatives, but maybe several other diseases such as CBD. For example, she points out that these bacteria have been found IN THE BRAINS of over 90% of those with AD symptoms that were tested, while NONE of the control samples had them. They may travel along the olfactory nerve, or other nerves or the lymphatic system and reach the brain. In the case of traveling long the olfactory nerve, that is consistent with the initial involvement of the olfactory lobe of the brain in the early symptoms of AD. Also, the presence of the bacteria have been shown to produce "neurofibrilary tangles" of tau proteins and "senile plaques" of amyloid beta protein. Exposure to Borrelia burgdorferi (Lyme disease) bacteria may lead to "hyperphosphorylation" of tau proteins.

Further searching leads me to possible treatments with antibiotics such as doxycycline, tetracycline, etc.

Anyway... read the papers. I think you will find them interesting.
Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.

Judith Miklossy

Correspondence: Judith Miklossy
Journal of Neuroinflammation 2011, 8:90 doi:10.1186/1742-2094-8-90

Published: 4 August 2011

Abstract (provisional)

It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis.

Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer's disease (AD).

Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill.

The results show a statistically significant association between spirochetes and AD (P = 1.5 x 10-17, OR = 20, 95% CI = 8-60, N = 247).
When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases.

Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls.

Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies.

Importantly, co-infection with several spirochetes occurs in AD.

The pathological and biological hallmarks of AD were reproduced in vitro.

The analysis of reviewed data following Koch's and Hill's postulates shows a probable causal relationship between neurospirochetosis and AD.

Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity.

As suggested by Hill, once the probability of a causal relationship is established prompt action is needed.

Support and attention should be given to this field of AD research.

Spirochetal infection occurs years or decades before the manifestation of dementia.

As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.

...

Conclusion

Various types of spirochetes, including B. burgdorferi, and six periodontal pathogen spirochetes ((T. socranskii, T. pectinovorum, T. denticola, T. medium, T. amylovorum and T. maltophilum) were detected in the brains of AD patients.

The pathological and biological hallmarks of AD, including increased AβPP level, Aβ deposition and tau phosphorylation were induced by spirochetes in vitro.

The statistical analysis showed a significant association between spirochetes and AD. The strongly significant association, the high risk factor and the analysis of data following Koch’s and Hill’s criteria, are indicative of a causal relationship between neurospirochetoses and AD.

Spirochetes are able to escape destruction by the host immune reactions and establish chronic infection and sustained inflammation.

In vivo studies with long exposure times will be necessary to efficiently study the sequence of events and the cellular mechanisms involved in spirochete induced AD-type host reactions and Aβ-plaque, “tangle” and “granulovacuolar” formation.

The characterization of all types of spirochetes and co-infecting bacteria and viruses is needed, in order to develop serological tests for the early detection of infection.

The pathological process is thought to begin long before the diagnosis of dementia is made therefore, an appropriate targeted treatment should start early in order to prevent dementia.

Persisting spirochetal infection and their persisting toxic components can initiate and sustain chronic inflammatory processes through the activation of the innate and adaptive immune system involving various signaling pathways.

In the affected brain the pathogens and their toxic components can be observed, along with host immunological responses.

The response itself is characteristic of chronic inflammatory processes associated with the site of tissue damage.

The outcome of infection is determined by the genetic predisposition of the patient, by the virulence and biology of the infecting agent
and by various environmental factors, such as exercise, stress and nutrition.

The accumulated knowledge, the various views, and hypotheses proposed to explain the pathogenesis of AD form together a comprehensive entity when observed in the light of a persisting chronic inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection.

As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Similarly to syphilis, one may prevent and eradicate dementia in AD.

The impact on healthcare costs and on the suffering of the patients would be substantial.
http://www.jneuroinflammation.com/content/8/1/90/abstract
http://www.jneuroinflammation.com/content/pdf/1742-2094-8-90.pdf


Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.
Miklossy J.
J Neuroinflammation. 2011 Aug 4;8(1):90. [Epub ahead of print]
Abstract

ABSTRACT: It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis. Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer's disease (AD). Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill. The results show a statistically significant association between spirochetes and AD (P = 1.5 x 10-17, OR = 20, 95% CI = 8-60, N = 247). When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases. Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls. Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies. Importantly, co-infection with several spirochetes occurs in AD. The pathological and biological hallmarks of AD were reproduced in vitro. The analysis of reviewed data following Koch's and Hill's postulates shows a probable causal relationship between neurospirochetosis and AD. Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity. As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Support and attention should be given to this field of AD research. Spirochetal infection occurs years or decades before the manifestation of dementia. As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.

PMID: 21816039 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21816039
More info in the provisional full text pdf: http://www.jneuroinflammation.com/content/pdf/1742-2094-8-90.pdf

[EDIT NOTE:  Include observations from full paper re. how this bacteria may follow the olfactory nerve into the brain, consistent with the first involvement of the olfactory lobe in the progression of AD.]
IN THE BRAIN... an infection starting in the mouth and traveling to the brain via the olfactory nerve like the three people who died this summer (2011) from that amoeba Naegleria fowleri:
http://www.washingtontimes.com/news/2011/aug/17/3-die-of-rare-brain-infection-from-amoeba-in-water/?utm_source=RSS_Feed&utm_medium=RSS

If the infection is in the brain, then that would explain why even after fixing all the problems with bad teeth and gums that people still decline. I would explain why people seem to do better when the take antibiotics. It would explain why Embrel helps for a time, but since it also suppresses the immune system, long-term use is disappointing. It does not explain all cases, but there are probably many paths that lead to the same destination.

I didn't realize that an infection with the bacteria that causes Lyme disease was so common, nor that the bacteria that cause periodontal disease was related, nor that syphilis bacteria was related!

But I'm always looking at the practical side: If this theory is correct, what does it allow us to do?

I wonder if methylene blue (Rember) actually kills off the bacteria?

I wonder if, when treating H.pylori, these other bugs are killed off in the process.

I'm thinking that while an infection may be the root cause of some portion of cases, maybe even most of the cases, there will probably be other causes.

I'm also thinking that while having tooth/gum problems may be a sign of severe infection, it probably doesn't take a huge colony of the bacteria to cause AD, but rather a few getting into the wrong place. I'm thinking this because no doubt there will be people who say that their LO had dentures or never had a problem with their teeth or gums. This may also be where "genetic predisposition" comes into play, not a predisposition to AD, but to a spirochete infection. There are probably people who are immune.

Some interesting discussions about this appear on these message boards:
"Alzheimer's disease - a neurospirochetosis?"
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/9014064208
"Alzheimer's disease - a neurospirochetosis."
http://www.freerepublic.com/focus/f-chat/2769347/posts


********************************************************************************************
Tetracyclines (Tetracycline, Doxycycline)

Could low-dosage of Doxycycline be considered for Alzheimer's disease treatment?
S.A. KAMER, and A.R. KAMER, New York University, New York, NY
July 2010

Objectives: Alzheimer's disease (AD) is a neurodegenerative disease primarily of the elderly, and treatment modalities are limited. AD is characterized by the presence of senile plaques with its main component amyloid â , neurofibrillary tangles with phosphophorylated tau protein, and neuronal loss. These pathological components as well as inflammation are hypothesized to be involved in the pathogenesis of AD.

When considering potential treatment modalities for AD, this pathogenesis should be considered. Periostat is a drug containing low dosages of Doxycycline and is used in long-term administration to treat periodontal disease without the side effects characterizing the anti-microbial doses of this medication.

The objective of this study is to evaluate the possible use of Periostat for treating AD by critically analyzing the existing literature.

Methods: a Medline search was undertaken using combinations of the following terms: doxycycline, tetracycline, minocycline, Alzheimer's disease, cognition, mild impairment cognition, metalloproteinase (MMP), amyloid, and inflammation. Then, the relevant papers were reviewed manually.

Results: the database search resulted in a total 301 papers containing the search terms. Further evaluation resulted in 45 papers containing relevant data. The studies evaluated were based on in vitro, animal, and clinical data.

Only one randomized control study was found. The review study found that tetracycline derivatives, including doxycycline:

cross the brain blood barrier;
b) have neuroprotective effects;
c) destabilize the amyloid fibrils to make them susceptible to proteolysis;
d) inhibit caspase-3 that has a role in tau protein neurotoxicity;
e) inhibit the production of proinflammatory molecules; and
f) slow cognitive decline.

However, untoward effects have also been reported related to tetracyclines anti-MMPs activities.

Conclusion: the available data suggest that in selective cases low dosage doxycycline may be effective in treating AD.
http://iadr.confex.com/iadr/2010barce/preliminaryprogram/abstract_140673.htm


A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease.
J Am Geriatr Soc. 2004 Mar;52(3):381-7.
Abstract

OBJECTIVES: To assess whether doxycycline and rifampin have a therapeutic role in patients with Alzheimer's disease (AD).

DESIGN: Randomized, triple-blind, controlled trial.

SETTING: Three tertiary care and two community geriatric clinics in Canada.

PARTICIPANTS: One hundred one patients with probable AD and mild to moderate dementia.

INTERVENTION: Oral daily doses of doxycycline 200 mg and rifampin 300 mg for 3 months.

MEASUREMENTS:
The primary outcome was a change in Standardized Alzheimer's Disease Assessment Scale cognitive subscale (SADAScog) at 6 months. Secondary outcomes were changes in the SADAScog at 12 months and tests of dysfunctional behavior, depression, and functional status.

RESULTS:
There was significantly less decline in the SADAScog score at 6 months in the antibiotic group than in the placebo group, (-2.75 points, 95% confidence interval (CI)=-5.28 to -0.22, P=.034). At 12 months, the difference between groups in the SADAScog was -4.31 points (95% CI=-9.17-0.56, P=.079). The antibiotic group showed significantly less dysfunctional behavior at 3 months. There was no significant difference in adverse events between groups (P=.34). There were no differences in Chlamydia pneumoniae detection using polymerase chain reaction or antibodies (immunoglobulin (Ig)G or IgA) between groups.

CONCLUSION: Therapy with doxycycline and rifampin may have a therapeutic role in patients with mild to moderate AD. The mechanism is unlikely to be due to their effect on C. pneumoniae. More research is needed to investigate these agents.

http://www.ncbi.nlm.nih.gov/pubmed/14962152


Anti-amyloidogenic activity of tetracyclines: studies in vitro.
Forloni G, Colombo L, Girola L, Tagliavini F, Salmona M.
Source: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. forloni@irfmn.mnegri.it
FEBS Lett. 2001 Jan 5;487(3):404-7.

Abstract

Cerebral deposition of beta-amyloid is a major neuropathological feature in Alzheimer's disease. Here we show that tetracyclines, tetracycline and doxycycline, classical antibiotics, exhibit anti-amyloidogenic activity. This capacity was determined by the exposure of beta 1-42 amyloid peptide to the drugs followed by the electron microscopy examination of the amyloid fibrils spontaneously formed and quantified with thioflavine T binding assay. The drugs reduced also the resistance of beta 1-42 amyloid fibrils to trypsin digestion. Tetracyclines not only inhibited the beta-amyloid aggregates formation but also disassembled the pre-formed fibrils. The results indicate that drugs with a well-known clinical profile, including activity in the central nervous system, are potentially useful for Alzheimer's therapy.
PMID: 11163366 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/11163366

My thought is, if as a teenager, my dermatologist can have me taking low dose tetracycline for 4 years to fight acne, why can't someone with dementia try it?


 ********************************************************************************************
Lyme Disease (Borrelia burgdorferi)

Chitosan Oligosaccharide has found a nich use in treatment of Lyme disease symptoms.
http://www.lyme-disease-research-database.com/alan-macdonald-transcription.html

Borrelia:
Borrelia and Alzheimer disease
Posted 21 August 2005 [to www.alzforum.org]
By Liz Shepherd

Here in South Carolina, several patients diagnosed with Alzheimer disease actually had DNA PCR positive Borrelia cultures grown from their brains. The symptoms for these illnesses do in fact overlap. Many psychiatrists now say that all brain disease is infectious. Have you actually LOOKED for a common denominator? Have all Alzheimer brains been checked for Borrelia? My guess is you may be very surprised to find out what is causing Alzheimer's.
http://www.alzforum.org/res/adh/hyp/default.asp#borrelia
LATE AND CHRONIC LYME DISEASE
- Sam T. Donta, MD* Prof. of Medicine, Divisions of Infectious Disease and BioMolecular Medicine Director, Lyme Disease Unit Boston University Medical Center, Boston, Massachusetts Corresponding author for proof and reprints: Sam T Donta MD 508-539-6666
Med Clin North Am 2002 Mar;86(2):341-9, vii.
http://www.canlyme.com/donta.html

Note the lengths of time recommended for treatments.


Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi.
Antimicrob Agents Chemother. 1995 May;39(5):1127-33.
Kersten A, Poitschek C, Rauch S, Aberer E.
SourceDepartment of Dermatology, University of Vienna, Austria.

Abstract

Antibiotic therapy with penicillin, doxycycline, and ceftriaxone has proven to be effective for the treatment of Lyme borreliosis. In some patients, however, it was noticed that borreliae can survival in the tissues in spite of seemingly adequate therapy. For a better understanding of this phenomenon, we investigated the different modes of degeneration of Borrelia burgdorferi suspensions during a 96-h exposure to various antibiotics. By dark-field microscopy and ultrastructural investigations, increasing blebbing and the gradual formation of granular and cystic structures could be followed during the exposure time. Although antibiotic concentrations at the MIC at which 90% of organisms are inhibited after 72 h were 80% or even greater, motile organisms were still present after incubation with penicillin and doxycycline but not after incubation with ceftriaxone. By transmission electron microscopy, intact spirochetal parts, mostly situated in cysts, were seen up to 96 h after exposure with all three antibiotics tested. According to experiences from studies with other spirochetes it is suggested that encysted borreliae, granules, and the remaining blebs might be responsible for the ongoing antigenic stimulus leading to complaints of chronic Lyme borreliosis.
PMID:7625800[PubMed - indexed for MEDLINE] PMCID: PMC162695
http://www.ncbi.nlm.nih.gov/pubmed/7625800?dopt=Abstract
 

Lyme disease info…

http://www.anapsid.org/lyme/

 

“Where fact and theory are incompatible, it is theory, not fact, that needs to be amended.”


[Message from Lyme].
Nord Med. 1993;108(5):157-8. [Article in Swedish]
Wahlberg P.
SourceAsvägen Mariehamn, Aland.

Abstract

The background to the discovery of Lyme disease teaches a salutary lesson. The symptoms and signs of this disease had been observed by doctors for a century, particularly in the Scandinavian countries, without anybody being able to draw the right conclusions. The first patients were identified in the USA by their relatives or by themselves. Recognition of their plight by the medical profession was chiefly due to the patients' tenacity. We must remember to pay attention to what patients tell us; they may often be right, even when they seem to be wrong. Where fact and theory are incompatible, it is theory, not fact, that needs to be amended. In all likelihood, we all from time to time observe disorders in our patients that are inconsistent with established scientific models, but which we nevertheless attempt to squeeze into these models. Such an approach is not uncommon in the history of medicine. The message from Lyme calls for humility and reflexion.
PMID:8497409[PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/8497409?dopt=AbstractPlus


********************************************************************************************
Infection and Immune System Response:

See also Helicobacter pylori
         HSV
         Inflammation
"A number of chronic diseases are in fact caused by one or more infectious agents. For example, stomach ulcers are caused by Helicobacter pylori, chronic lung disease in newborns and chronic asthma in adults are both caused by Mycoplasmas and Chlamydia pneumonia, while some other pathogens have been associated with atherosclerosis. The realization that pathogens can produce slowly progressive chronic diseases has opened new lines of research into Alzheimer's disease."

Here are some excerpts from an article found on ScienceDaily.com:
Cold Sore Virus Linked To Alzheimer's Disease: New Treatment, Or Even Vaccine Possible
ScienceDaily (Dec. 7, 2008)

"Professor Itzhaki explains: "We suggest that HSV1 enters the brain in the elderly as their immune systems decline and then establishes a dormant infection from which it is repeatedly activated by events such as stress, immunosuppression, and various infections."

"The ensuing active HSV1 infection causes severe damage in brain cells, most of which die and then disintegrate, thereby releasing amyloid aggregates which develop into amyloid plaques after other components of dying cells are deposited on them."

"Her colleague Dr Matthew Wozniak adds: "Antiviral agents would inhibit the harmful consequences of HSV1 action; in other words, inhibit a likely major cause of the disease irrespective of the actual damaging processes involved, whereas current treatments at best merely inhibit some of the symptoms of the disease..."

"They believe the herpes simplex virus is a significant factor in developing the debilitating disease and could be treated by antiviral agents such as acyclovir, which is already used to treat cold sores and other diseases caused by the herpes virus."
http://www.sciencedaily.com/releases/2008/12/081207134109.htm


Another earlier article:
New Evidence Found Linking Herpes And Alzheimer’s
ScienceDaily (May 12, 2000)
"Could Lead to New Treatments Targeting the Herpes Virus"

"Researchers have long suspected a connection between the herpes virus and Alzheimer’s disease. A new study provides a potential explanation that could lead to development of a vaccine to prevent the disease or new drugs to treat it, according to the researchers. The study appears in the May 16 issue of Biochemistry, a peer-reviewed publication of the American Chemical Society, the world’s largest scientific society."

"Researchers at the University of California, Irvine, demonstrated that a synthetic protein that resembles the herpes simplex 1 virus (HSV-1) mimics the structure and function of a protein called beta-amyloid, a toxic agent that accumulates in the brains of Alzheimer’s patients."

"Genetic sequencing revealed that two-thirds of a portion of the viral protein is identical to the beta-amyloid protein. The researchers showed that, like beta-amyloid, it could kill brain neurons, a key feature in the development of Alzheimer’s. Moreover, in laboratory experiments, the viral protein formed abnormal twisted fibers like those found in the brains of Alzheimer’s patients — the definitive hallmark of the disease..."
http://www.sciencedaily.com/releases/2000/05/000512083302.htm

And, another...
Cold Sore Virus Might Play Role In Alzheimer's
ScienceDaily (Jan. 3, 2007)
"A gene known to be a major risk factor for Alzheimer's disease puts out the welcome mat for the virus that causes cold sores, allowing the virus to be more active in the brain compared to other forms of the gene..."
http://www.sciencedaily.com/releases/2007/01/070103110103.htm

From these articles (I suggest reading the full articles and others you can find), it seems to be a reasonable theory that this HSV1 virus invades the brain as one's immune system weakens with age, stress or truma. Infected cells then expire, leaving behind amyloid beta (AB). Some people's central nervous system (NS) are probably better than other people's at removing this amyloid beta. So, most people develop the classic characteristics of AD, which are loss of brain mass, clumps of AB, and intracellular tau tangles. Others, whose CNS clears out the AB still suffer the loss of brain mass as the disease ravages the brain, and other proteins accumulate, such as just the tau tangles or clumps of tau.  Could this be behind CBD?

What this theory says to me is that there is a chance that many of what today seem like separate neurodegenerative diseases may actually be manifestations of the same root cause: A virus. But it also says that most of the things we have been trying will ultimately fail. Enbrel addresses inflammatory responses. Methylene blue and cinnamon attack tau and maybe help neurons live longer. MCT's (coconut oil) and cinnamon address sugar metabolism. Lithium fights tau corruption. Curcumin is used in the hopes of reducing the AB load. Likewise with all of the other the pharmaceuticals and supplements we have discussed and had such hopes for.

But, none of these attack what might be the root cause, HSV1; and if they don't, then their positive effects are all doomed to eventually be overwhelmed by the virus' insatiable hunger for brain cells. It is every bit as horrific as the plot from some "B" science fiction movie.

Does anyone have experience with this drug they mention in the first article, acyclovir? What is the likelihood that a physician would prescribe this drug to someone suspected of having AD just to see if it helps?

[NOTE:  Jan. 17, 2009: Recently, some people have mentioned in posts to some discussion forums that curcumin, resveratrol and lauric acid (coconut oil!) may fight the HSV-1 virus. Need to find more info and links to sources.]

I've read before about urinary tract infections causing a sudden worsening of AD symptoms. The question that came to my mind was, why does this happen?

I think I have a possible answer. And with this answer comes the opportunity to do something for someone suffering from AD.

There was a small two-year study done in Greece that was recently published. 50 subjects with AD symptoms were tested for the presence of a Helicobacter pylori (Hp) infection (the bacteria that is said to cause most stomach ulcers). It turned out that nearly 90% of the subjects had H.pylori. So the researchers treated the infection. Eradication of the bacteria was successful in about 85% of the cases. The amazing thing was that in ALL of the 85% where the eradication of the H.pylori was successful, their AD symtoms did not progress over the 2 years of the study, and in fact, their mental abilities improved somewhat. Even though this was a very small study with only 50 participants, to me the results say that there might be something to this that we can use.

How can an H.pylori infection of the stomach affect the brain? The researchers speculated that the body produces substances in its fight against the bacteria that might have deleterious side effects when the blood carries them to the brain. One of these substances is called "tumor necrosis factor alpha", (TNF-alpha).

Last year, there was some excitement over a drug being researched called "Rember". It was theorized that this drug acted directly on the tau protein of the neurons to prevent them from becoming corrupted, or to even dissolve clumps and tangles of currupted tau that had already formed. The researchers were disappointed to discover that the highest dose pill they used was not effective because, unlike its smaller dose cousins, the 100mg pill dissolved in the intestines rather than the stomach. What is "Rember"? Well, it is essentially methylene blue. And methylene blue happens to be an antibiotic known to kill off H.pylori.

Let's go to the other side of the Earth for another piece of the puzzle. In California there is this controversial physician, Dr. Tobinick, who discovered by accident that when he injected the arthritis drug Enbrel into the spines of his patients suffering from spinal arthritis, sometimes their AD symptoms would suddenly improve in a matter of minutes. How could this happen? Well, Enbrel blocks the effects of TNF!

What does this have to do with urinary tract infections? Could a UTI cause the body to produce TNF? A quick search of the Internet with Google using the two phrases "tumor necrosis factor" "urinary tract infection" makes me think that, yes indeed, we may have the connection. The body produces TNF in its fight against the UTI bacteria, which is then circulated by the blood to the brain.

What can you do with this? Find out if your loved one with AD symptoms has a chronic infection. Look for H.pylori, a UTI, maybe even pockets of infection in the jaw left over from a tooth problem. Periodontal (gum) disease may increase the risk of cognitive dysfunction associated with Alzheimer's disease in healthy individuals as well as in those who already are cognitively impaired. Another possibility is the presence of Lyme disease. If they have one of these infections, get it treated.
The Pathogen Hypothesis (Live Discussion on www.alzforum.org)
Moderator’s summary: Pathogens as a cause of Alzheimer’s disease
By June Kinoshita

The notion that microbes such as herpes simplex virus 1 (HSV1) and Chlamydophila pneumoniae (Cp) could be a causal factor in Alzheimer’s diseases would probably be viewed by the main stream of AD researchers as being beyond the pale. Although a small body of recent findings has reported strikingly strong associations between these pathogens and AD [1,7], subsequent attempts to replicate the findings have met with mixed results (discussed in [10]). At this juncture, it might be convenient to dismiss the hypothesis, but as both sides of this debate session agreed, there are plausible reasons for these discrepancies that deserve to be resolved through further research. While opinions diverged on the strength of evidence for and against the hypothesis, there was a consensus that the possibility of common infectious agents causing such a widespread scourge of old age is one that is too important to ignore.
http://www.alzforum.org/res/for/journal/balin/default.asp
Among Older Patients, Severe Sepsis Associated With Development of Cognitive and Functional Disability
ScienceDaily (Oct. 27, 2010)
Older adults who survived severe sepsis were more likely to develop substantial cognitive impairment and functional disability, according to a study in the October 27 issue of JAMA... The researchers found that the prevalence of moderate to severe cognitive impairment increased 10.6 percentage points among patients who survived severe sepsis, and their odds of acquiring moderate to severe cognitive impairment were 3.3 times higher. Also, a high rate of new functional limitations was seen following sepsis, with an additional average increase of 1.5 new functional limitations per person among those with no or mild to moderate pre-existing functional limitations.

Nonsepsis general hospitalizations were associated with no change in moderate to severe cognitive impairment and with the development of fewer new limitations.

"Cognitive and functional declines of the magnitude seen after severe sepsis are associated with significant increases in caregiver time, nursing home admission, depression, and mortality. These data argue that the burden of sepsis survivorship is a substantial, underrecognized public health problem with major implications for patients, families, and the health care system."...
http://www.sciencedaily.com/releases/2010/10/101026161241.htm


********************************************************************************************

TNF-Alpha

See also Enbrel
         Chitosan
         Cat's Claw
         Cinnamon
         Curcumin
         Inflammation
         NT-020 references in AFA

Supplements that might block TNF-Alpha
Enbrel
Water-soluble chitosan (chitosan oligosaccharaide)
Cat's Claw
Cinnamon (?)
Curcumin (?)
NT-020 (See references in AFA)

Note:  The body uses TNF-alpha to fight infections.  Blocking tumor necrosis factor-alpha (an inflammation-causing cytokine), raises the risk of activating a latent infection such as tuberculosis due to the importance of this cytokine in the immune defense against them.

From the Alz.org message board "Medications/Treatments for Alzheimer's and Other Related Dementias"

Posted August 05, 2008 12:11 PM
...I would love to see that replicated by a supplement that is relatively free of side-effects such as Chitosan oligosaccharide, cats, claw, or whatever. So I'm looking at these and others to see if there is yet more than one road that leads to Rome so to speak. I've always heard there are many. I bet there is. Right now I'm kind of excited about cats claw (cc) as it passes through the BBB in 2 minutes. There appears to be very limited experience with it on AD patients so we don't really know what sort of response it might elicit from an AD patient, yet it has good data showing it works by TNF-alpha suppression...and it has been reported to be as safe as coffee. Nevertheless some side-effects have been reported that might involve kidney function...so maybe not as safe as coffee. Also very rapid response of cc has been reported in other inflammatory diseases that it has been used for in human patients...
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/4081064272?r=3891056613#3891056613

Some more references to earlier research:

Elevated circulating tumor necrosis factor levels in Alzheimer's disease.
Fillit H, Ding WH, Buee L, Kalman J, Altstiel L, Lawlor B, Wolf-Klein G.
Neurosci Lett. 1991 Aug 19;129(2):318-20.

Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients.
Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MB.
PNAS 1986;83(18): 7089-7093

Role of human immunodeficiency virus and cytomegalovirus in AIDS encephalitis.
Wiley CA, Nelson JA. Am J Pathol.
1988 October; 133(1): 73–81.

 Tumor necrosis factor identified in multiple sclerosis brain.
Hofman FM, Hinton DR, Johnson K, Merrill JE. J
Exp Med. 1989 August 1; 170(2): 607–612.

http://www.pnas.org/cgi/doi/10.1073/pnas.1014557107

See Haark 2004, Medeiros 2007, Riazi 2008, McAfoose and Baume 2008, and Leisz 2009.

Breakthrough or False Hope? Etanercept Case Report Draws Scrutiny
http://www.alzforum.org/new/detail.asp?id=1738


Targeting TNF-Alpha to Elucidate and Ameliorate Neuroinflammation in Neurodegenerative Diseases.
CNS Neurol Disord Drug Targets. 2011 Feb 2. [Epub ahead of print]
Frankola KA, Greig NH, Luo W, Tweedie D.
PMID: 21288189


Systemic inflammation is associated with MCI and its subtypes: the Sydney Memory and Aging Study.
Dement Geriatr Cogn Disord. 2010;30(6):569-78. Epub 2011 Jan 20.
PMID: 21252552


Tumor necrosis factor-alpha mediated signaling in neuronal homeostasis and dysfunction.
Cell Signal. 2010 Jul;22(7):977-83. Epub 2010 Jan 21.
Park KM, Bowers WJ.

Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Abstract
Tumor necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory molecule, which upon engagement with its cognate receptors on target cells, triggers downstream signaling cascades that control a number of cellular processes related to cell viability, gene expression, ion homeostasis, and synaptic integrity. In the central nervous system (CNS), TNF-alpha is produced by brain-resident astrocytes, microglia, and neurons in response to numerous intrinsic and extrinsic stimuli. This review will summarize the key events that lead to TNF-alpha elaboration in the CNS, and the effects that these inflammatory signals impart on neuronal signaling in the context of homeostasis and neuropathology.
PMID: 20096353

********************************************************************************************

Chitosan (Water-soluble Chitosan, chitosan oligosaccharide)

Here is a Pubmed citation:
Inhibitory effect of high molecular weight water-soluble chitosan on hypoxia-induced inflammatory cytokine production.
http://www.ncbi.nlm.nih.gov/pubmed/12736519

It says that that WSC (water-soluble chitosan) inhibited "TNF-alpha". I assume there is a "TNF-beta", etc. What brand of TNF does etanercept inhibit?

Interestingly, they used desferrioxamine (desferral) to create the elevated levels of TNF. But, other researchers in Canada have used desferral to arrest the progression of AD. So, *there's* a puzzle...

Desferral is used primarily as a powerful iron chelator, on the same order as phytic acid (IP6).

This research was done in Japan. I wonder if WSC is available in the US?

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0G-451DD9T-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=ee4019d7850933a86133b8fc20be802d

From the Alz.org message board "Medications/Treatments for Alzheimer's and Other Related Dementias":
Posted July 23, 2008 01:43 PM
After very extensive review of nearly everything out there for treatment of AD, I have come to the conclusion that water-soluble chitosan (WSC) is the only non-drug "supplement" out there that targets TNF. Let me say that again...WSC targets TNF in the brain. Because it appears to be safe, has never been linked to shell-fish allergies (a topic addressed in the chitosan literature) is marketed in edible form, and is used as a general energy and anti-aging tonic, mostly in China, and has animal model AD research showing that it targets TNF in a manner similar to Enbrel, I think it is worthy of trying...
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/4081064272?r=2661005413#2661005413

Sources???:  http://en.haidebei.com/newEbiz1/EbizPortalFG/portal/html/ProductInfoExhibit.html?ProductInfoExhibit_ProductID=c373e911f56523978f6e9d2e0a9b4fa4&ProductInfoExhibit_isRefreshParent=false

             http://www.outletnutrition.com/713947559905.html

             http://heavenshealth.com/benefits.htm

             This is a US supplier of water soluble chitosan.
             http://www.alibaba.com/countrysearch/US-suppliers/Water_Soluble_Chitosan.html


********************************************************************************************

Cat's Claw  (Uncaria tomentosa, Una de Gato)

The content of this topic was moved to Notes_II

********************************************************************************************


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?

********************************************************************************************


Green Tea  (EGCG, epigallocatechin gallate)

See also Oligomers,

Green Tea Has Rejuvenating Effect on Damaged Brain Cells
Researchers at the Technion Institute of Science in Haifa have shown that feeding green tea extract to mice with Parkinson's and Alzheimer's disease protects brain cells from dying, and helps 'rescue' already damaged neurons in the brain...
http://alzheimersweekly.com/content/green-tea-has-rejuvenating-effect-damaged-brain-cells


EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity. Bieschke J, Russ J, Friedrich RP, Ehrnhoefer DE, Wobst H, Neugebauer K, Wanker EE.
Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7710-5.

Abstract

Protein misfolding and formation of beta-sheet-rich amyloid fibrils or aggregates is related to cellular toxicity and decay in various human disorders including Alzheimer's and Parkinson's disease. Recently, we demonstrated that the polyphenol (-)-epi-gallocatechine gallate (EGCG) inhibits alpha-synuclein and amyloid-beta fibrillogenesis. It associates with natively unfolded polypeptides and promotes the self-assembly of unstructured oligomers of a new type. Whether EGCG disassembles preformed amyloid fibrils, however, remained unclear. Here, we show that EGCG has the ability to convert large, mature alpha-synuclein and amyloid-beta fibrils into smaller, amorphous protein aggregates that are nontoxic to mammalian cells. Mechanistic studies revealed that the compound directly binds to beta-sheet-rich aggregates and mediates the conformational change without their disassembly into monomers or small diffusible oligomers. These findings suggest that EGCG is a potent remodeling agent of mature amyloid fibrils.
http://www.ncbi.nlm.nih.gov/pubmed/20385841?dopt=Abstract


Alzheimer Research Forum Comment by:  Jun Tan, Terrence Town      
    Submitted 27 April 2010     Posted 27 April 2010
   
...Erich Wanker and colleagues show that EGCG, the main polyphenolic constituent of green tea, reduces cellular toxicity by inhibiting β amyloid and α-synuclein fibrillogenesis...
http://www.alzforum.org/pap/annotation.asp?powID=101554


Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1.
Am J Clin Nutr. 2006 Feb;83(2):355-61.

Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, Awata S, Nagatomi R, Arai H, Tsuji I.

Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

Abstract

BACKGROUND: Although considerable experimental and animal evidence shows that green tea may possess potent activities of neuroprotection, neurorescue, and amyloid precursor protein processing that may lead to cognitive enhancement, no human data are available.

OBJECTIVE: The objective was to examine the association between green tea consumption and cognitive function in humans.

DESIGN: We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment (CGA) conducted in 2002. The subjects were 1003 Japanese subjects aged > or =70 y. They completed a self-administered questionnaire that included questions about the frequency of green tea consumption. We evaluated cognitive function by using the Mini-Mental State Examination with cutoffs of <28, <26, and <24 and calculated multivariate-adjusted odds ratios (ORs) of cognitive impairment.

RESULTS: Higher consumption of green tea was associated with a lower prevalence of cognitive impairment. At the <26 cutoff, after adjustment for potential confounders, the ORs for the cognitive impairment associated with different frequencies of green tea consumption were 1.00 (reference) for < or =3 cups/wk, 0.62 (95% CI: 0.33, 1.19) for 4-6 cups/wk or 1 cup/d, and 0.46 (95% CI: 0.30, 0.72) for > or =2 cups/d (P for trend = 0.0006). Corresponding ORs were 1.00 (reference), 0.60 (95% CI: 0.35, 1.02), and 0.87 (95% CI: 0.55, 1.38) (P for trend = 0.33) for black or oolong tea and 1.00 (reference), 1.16 (95% CI: 0.78, 1.73), and 1.03 (95% CI: 0.59, 1.80) (P for trend = 0.70) for coffee. The results were essentially the same at cutoffs of <28 and <24.

CONCLUSION: A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humans.

PMID: 16469995 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/16469995
Free article: American Journal of Clinical Nutrition, Vol. 83, No. 2, 355-361, February 2006
              http://www.ajcn.org/content/83/2/355.long
http://www.ncbi.nlm.nih.gov/pubmed/20617284

http://www.ncbi.nlm.nih.gov/pubmed/19828710

http://www.ncbi.nlm.nih.gov/pubmed/19793850

http://www.ncbi.nlm.nih.gov/pubmed/18614745

http://www.ncbi.nlm.nih.gov/pubmed/16469995

http://www.ncbi.nlm.nih.gov/pubmed/16372926
Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study.
http://www.ncbi.nlm.nih.gov/pubmed/16968850


Improvement of periodontal status by green tea catechin using a local delivery system: a clinical pilot study.
J Periodontal Res. 2002 Dec;37(6):433-8.
Hirasawa M, Takada K, Makimura M, Otake S.
Source: Department of Microbiology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba Japan

Abstract

The purpose of this study was to determine the usefulness of green tea catechin for the improvement of periodontal disease. The minimum inhibitory concentration (MIC) and bactericidal activity of green tea catechin against black-pigmented, Gram-negative anaerobic rods (BPR) were measured. Hydroxypropylcellulose strips containing green tea catechin as a slow release local delivery system were applied in pockets in patients once a week for 8 weeks. The clinical, enzymatic and microbiological effects of the catechin were determined. Green tea catechin showed a bactericidal effect against Porphyromonas gingivalis and Prevotella spp. in vitro with an MIC of 1.0 mg/ml. In the in vivo experiment, the pocket depth (PD) and the proportion of BPR were markedly decreased in the catechin group with mechanical treatment at week 8 compared with the baseline with significant difference. In contrast, PD and BPR were similar to the baseline and the value at the end of the experimental period in the placebo sites of scaled groups. The peptidase activities in the gingival fluid were maintained at lower levels during the experimental period in the test sites, while it reached 70% of that at baseline in the placebo sites. No morbidity was observed in the placebo and catechin groups without mechanical treatment. Green tea catechin showed a bactericidal effect against BPR and the combined use of mechanical treatment and the application of green tea catechin using a slow release local delivery system was effective in improving periodontal status.
PMID:12472837[PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/12472837
http://ovoh.net/Files/PerioAndGreenTea.pdf
 


Inhibition of periodontopathogen-derived proteolytic enzymes by a high-molecular-weight fraction isolated from cranberry
Journal of Antimicrobial Chemotherapy (2006) 57, 685–690
doi:10.1093/jac/dkl031
Advance Access publication 10 February 2006

Charles Bodet, Marilou Piche, Fatiha Chandad and Daniel Grenier

Results: NDM dose-dependently inhibited the proteinases of P. gingivalis, T. forsythia and T. denticola [a spirochete] as well as type I collagen and transferrin degradation by P. gingivalis.
http://jac.oxfordjournals.org/content/57/4/685.full.pdf

[Need PubMed]

 
Inhibition of host- and bacteria-derived proteinases by natural anthocyanins
J. Santos1, V. D. La1, C. Bergeron2, D. Grenier1Article first published online: 21 APR 2011
DOI: 10.1111/j.1600-0765.2011.01372.
http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0765.2011.01372.x/abstract


Google search:  http://www.google.com/#sclient=psy&hl=en&source=hp&q=%22green+tea%22+bactericidal+periodontal+denticola&pbx=1&oq=%22green+tea%22+bactericidal+periodontal+denticola&aq=f&aqi=&aql=1&gs_sm=e&gs_upl=140l3984l1l4547l9l9l0l0l0l0l688l3295l0.1.3.2.1.2l9l0&bav=on.2,or.r_gc.r_pw.&fp=d4517628c849646&biw=1001&bih=707&safe=images


********************************************************************************************
Tooth/Gum Health

Tooth Loss May Be Linked to Memory Loss
Gum infection may cause inflammation that affects the brain, researcher suggests
TUESDAY, Jan. 4 (HealthDay News)
http://www.businessweek.com/lifestyle/content/healthday/648432.html

The Periodontal Solution – Healthy Gums Naturally

http://www.theintegrativedentist.com/oralirrigation.html

http://www.theintegrativedentist.com/references.html


Tooth Decay
"Most people over 60 have root cavities as a result of gum disease ... Although hydrogen peroxide is bacteriocidal and sodium bicarbonate is bacteriostatic, there ..."
http://www.dentalgentlecare.com/tooth_decay.htm


See BANA Bacterial Home Test. http://mizar5.com/bana1.html

Dr. Paul H. Keyes


Dr. Keyes is the founder of  the International Dental Health Foundation

Education: D.D.S., University of Pennsylvania School of Dental Medicine (1941); B.A., University of Rochester (1944); M.S. in Anatomy, University of Rochester (1945); Fellowship in Orthodontics, Harvard University School of Dental Medicine (1948).

[Some interesting ideas, but need references for some claims…]

http://mizar5.com/keyes.html


In many cases, sodium bicarbonate was found to be effective against periodontal microorganisms. In a study by Rams et al., a five-minute exposure to sodium bicarbonate quickly immobilized spirochetes and motile rods. (9)

(9.) Rams TE, Keyes PH, Wright WE, Howard SA. Long-term effects of microbiologically modulated periodontal therapy on advanced adult periodontitis. J Am Dent Assoc. 1985;111(3): 429-41.
Long-term effects of microbiologically modulated periodontal therapy on advanced adult periodontitis.
Rams TE, Keyes PH, Wright WE, Howard SA.
J Am Dent Assoc. 1985 Sep;111(3):429-41.
PMID:2995468[PubMed]
[ NEED LINK ]
 
The use of phase-contrast microscopy and chemotherapy and the diagnosis and treatment of periodontal lesions-an initial report.
Keyes PH, Wright WE, Howard SA.
Quintessence Int. 1978;9(1): 51-56.

http://www.smartahealth.com/gum_disease.html
The use of sodium bicarbonate in oral hygiene products and practice.
E Newbrun
Department of Stomatology, University of California, San Francisco, San Francisco, California, USA.

Early dentifrices contained natural ingredients, mostly in coarse particle form, and were quite abrasive. Salts, either sodium chloride, sodium bicarbonate, or a mixture of both, have also been used for tooth cleaning because of their ready availability and low cost. Because of both their relatively low intrinsic hardness and their high solubility, another advantage is low abrasivity. Their biggest disadvantage is a salty, unpalatable taste. Many modern dentifrices that contain sodium bicarbonate, either as the sole abrasive or one of several, disguise the saltiness with flavoring and sweetening agents. An almost inverse relationship exists between the percentage of baking soda in a dentifrice and its abrasivity. Sodium bicarbonate has no anticaries activity per se but is compatible with fluoride. In high concentrations, sodium bicarbonate is bactericidal against most periodontal pathogens. Most clinical studies have not found significant differences in periodontal response to baking soda as compared with other commercial dentifrices, probably because of its rapid clearance from the gingival sulcus. Sodium bicarbonate may not be the "magic bullet" for curing dental diseases, but its safety (if ingested), low abrasivity, low cost, and compatibility with fluoride make it a consummate dentifrice ingredient. Community Dent Oral Epidemiol. 1980 ;8 (5):230-6  7006899  Cit:2
http://lib.bioinfo.pl/meid:84192
Antimicrobial Properties of Hydrogen Peroxide and Sodium Bicarbonate Individually and in Combination Against Selected Oral, Gram-negative,Fa
cultative Bacteria
K. T. MIYASAKI, R. J. GENCO, and M. E. WILSON
http://jdr.sagepub.com/content/65/9/1142.full.pdf
Keyes Technique: The Fallacy of the Usage of Hydrogen Peroxide in Periodontal Therapy
http://www.drbui.com/arthydrogenperoxide.html

********************************************************************************************
Herpes Simplex Virus (HSV-1)

See also Infection and the Immune System Response
         Lysine
         Curcumin
New Evidence Found Linking Herpes And Alzheimer’s
ScienceDaily (May 12, 2000)
"Could Lead to New Treatments Targeting the Herpes Virus"

"Researchers have long suspected a connection between the herpes virus and Alzheimer’s disease. A new study provides a potential explanation that could lead to development of a vaccine to prevent the disease or new drugs to treat it, according to the researchers. The study appears in the May 16 issue of Biochemistry, a peer-reviewed publication of the American Chemical Society, the world’s largest scientific society."

"Researchers at the University of California, Irvine, demonstrated that a synthetic protein that resembles the herpes simplex 1 virus (HSV-1) mimics the structure and function of a protein called beta-amyloid, a toxic agent that accumulates in the brains of Alzheimer’s patients."

"Genetic sequencing revealed that two-thirds of a portion of the viral protein is identical to the beta-amyloid protein. The researchers showed that, like beta-amyloid, it could kill brain neurons, a key feature in the development of Alzheimer’s. Moreover, in laboratory experiments, the viral protein formed abnormal twisted fibers like those found in the brains of Alzheimer’s patients — the definitive hallmark of the disease..."
http://www.sciencedaily.com/releases/2000/05/000512083302.htm

Another...
Cold Sore Virus Might Play Role In Alzheimer's
ScienceDaily (Jan. 3, 2007)
"A gene known to be a major risk factor for Alzheimer's disease puts out the welcome mat for the virus that causes cold sores, allowing the virus to be more active in the brain compared to other forms of the gene..."
http://www.sciencedaily.com/releases/2007/01/070103110103.htm

Alzheimer’s Disease Vaccine on the Horizon
December 15, 2010
...Infectious agents are normally known for causing acute illnesses, but some have been implicated as the cause of chronic diseases, including human papillomavirus in cervical cancer and the bacterium Helicobacter pylori in stomach ulcers, which has led to the use of vaccines and antimicrobial agents to treat chronic diseases. In the last decade, Herpes simplex virus type 1 (HSV1) has been increasingly associated with the development of AD... HSV1 does not cause AD on its own. There are likely host factors that alter the risks for developing AD...
http://brainblogger.com/2010/12/15/alzheimer’s-disease-vaccine-on-the-horizon/

From these articles (I suggest reading the full articles and others you can find), it seems to be a reasonable theory that this HSV1 virus invades the brain as one's immune system weakens with age, stress or truma. Infected cells then expire, leaving behind amyloid beta (AB). Some people's central nervous system (NS) are probably better than other people's at removing this amyloid beta. So, most people develop the classic characteristics of AD, which are loss of brain mass, clumps of AB, and intracellular tau tangles. Others, whose CNS clears out the AB still suffer the loss of brain mass as the disease ravages the brain, and other proteins accumulate, such as just the tau tangles or clumps of tau.  Could this be behind CBD?

What this theory says to me is that there is a chance that many of what today seem like separate neurodegenerative diseases may actually be manifestations of the same root cause: A virus. But it also says that most of the things we have been trying will ultimately fail. Enbrel addresses inflammatory responses. Methylene blue and cinnamon attack tau and maybe help neurons live longer. MCT's (coconut oil) and cinnamon address sugar metabolism. Lithium fights tau corruption. Curcumin is used in the hopes of reducing the AB load. Likewise with all of the other the pharmaceuticals and supplements we have discussed and had such hopes for.

But, none of these attack what might be the root cause, HSV1; and if they don't, then their positive effects are all doomed to eventually be overwhelmed by the virus' insatiable hunger for brain cells. It is every bit as horrific as the plot from some "B" science fiction movie.
Here is the link to a study Michigan State University about curcumin and HSV-1:
Curcumin inhibits herpes simplex virus immediate-early gene expression by a mechanism independent of p300/CBP histone acetyltransferase activity.
Virology. 2008 Apr 10;373(2):239-47. Epub 2008 Jan 14.
Kutluay SB, Doroghazi J, Roemer ME, Triezenberg SJ.

Graduate Program in Cell and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
Abstract

Curcumin, a phenolic compound from the curry spice turmeric, exhibits a wide range of activities in eukaryotic cells, including antiviral effects that are at present incompletely characterized. Curcumin is known to inhibit the histone acetyltransferase activity of the transcriptional coactivator proteins p300 and CBP, which are recruited to the immediate early (IE) gene promoters of herpes simplex virus type 1 (HSV-1) by the viral transactivator protein VP16. We tested the hypothesis that curcumin, by inhibiting these coactivators, would block viral infection and gene expression. In cell culture assays, curcumin significantly decreased HSV-1 infectivity and IE gene expression. Entry of viral DNA to the host cell nucleus and binding of VP16 to IE gene promoters was not affected by curcumin, but recruitment of RNA polymerase II to those promoters was significantly diminished. However, these effects were observed using lower curcumin concentrations than those required to substantially inhibit global H3 acetylation. No changes were observed in histone H3 occupancy or acetylation at viral IE gene promoters. Furthermore, p300 and CBP recruitment to IE gene promoters was not affected by the presence of curcumin. Finally, disruption of p300 expression using a short hairpin RNA did not affect viral IE gene expression. These results suggest that curcumin affects VP16-mediated recruitment of RNA polymerase II to IE gene promoters by a mechanism independent of p300/CBP histone acetyltransferase activity.

PMID: 18191976 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/18191976
Free full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668156/?tool=pubmed
The Pathogen Hypothesis (Live Discussion on www.alzforum.org)
Moderator’s summary: Pathogens as a cause of Alzheimer’s disease
By June Kinoshita

The notion that microbes such as herpes simplex virus 1 (HSV1) and Chlamydophila pneumoniae (Cp) could be a causal factor in Alzheimer’s diseases would probably be viewed by the main stream of AD researchers as being beyond the pale. Although a small body of recent findings has reported strikingly strong associations between these pathogens and AD [1,7], subsequent attempts to replicate the findings have met with mixed results (discussed in [10]). At this juncture, it might be convenient to dismiss the hypothesis, but as both sides of this debate session agreed, there are plausible reasons for these discrepancies that deserve to be resolved through further research. While opinions diverged on the strength of evidence for and against the hypothesis, there was a consensus that the possibility of common infectious agents causing such a widespread scourge of old age is one that is too important to ignore.
http://www.alzforum.org/res/for/journal/balin/default.asp
Another Look at Herpes Simplex
Chronic Flare-Ups Pose Harm to Brain
Cincinnati Children's Hospital Medical Center
Fall 2010
A virus that most of us carry but think little about should probably make us think twice, says Nancy Sawtell, PhD.

Sawtell, a researcher in the Division of Infectious Diseases, has been studying herpes simplex virus (HSV) for two decades. She, together with her collaborator Richard Thompson, PhD, at the University of Cincinnati College of Medicine, have discovered a number of things about the virus – and hope that what they have learned will change our largely cavalier attitude about it.

“This virus, which most of us have, has the potential to be wicked,” Sawtell says. “We have not done a good job educating people about it.” In fact, “wicked” might be an understatement. Once we contract HSV – and estimates are that between 70 and 90 percent of the world population has it – we can’t get rid of it. The virus remains latent in the nervous system for a lifetime, but periodically can flare up to cause anything from mild cold sores to genital rashes to encephalitis, blindness and even death. HSV may even have a link to Alzheimer’s disease, Sawtell says...

The Alzheimer's Connection

Sawtell wants to stop this lytic cycle because she has evidence that repeated inflammation caused by the virus harms the central nervous system.

“Having a latent virus that periodically reactivates in your central nervous system can’t be a good thing,” she says.

Sawtell is investigating whether repeated cycles of inflammation might lead to Alzheimer’s disease for some individuals. The idea was brought to her attention by British researcher Ruth Itzhaki, PhD.

“She had a hypothesis that carrying this chronic latent infection in your brain, when combined with a certain genetic background, represents a very high risk of developing Alzheimer’s,” Sawtell says.

By her own admission, Sawtell “was skeptical” about the idea. But Itzhaki’s research found that individuals who have a combination of latent HSV in the brain and the genetic variant APOE 4 have increased risk of acquiring Alzheimer’s disease. “And this work is fairly convincing” says Sawtell, “but demonstrating causality is difficult without an animal model.” So Sawtell began working with mice in which the human APOE 4 allele was knocked in, and infected them with HSV.

“A lot more virus got into the brains of the animals with the APOE 4 allele,” she says.

Sawtell also induced reactivation of the virus episodically over a long period of time to see what happened in the mouse’s central nervous system...
http://www.cincinnatichildrens.org/health/subscribe/ResearchHorizons/archives/2010/fall/herpes-simplex.htm


Lauric Acid:
Apparently the nerves to the face originate deep in the brain.  It is very conceivable that a cold sore outbreak on the skin could travel along the nerve path and back deep into the brain. The neurons have thousands of connections to other neurons and the virus could spread that way to other cells. See Dr. Ruth Itzhaki's research.  It has shown the presence of DNA of the herpes virus in beta-amyloid plaques in people with APOE4 gene. For people without the APOE4 gene, it could be another infection or toxin that results in AD or other neurodegenerative diseases. The lauric acid in coconut oil also kills helicobacter pylori, candida and other fungi, and other viruses with lipid capsules, such as HIV and other members of the herpes virus family.

See refs at: http://www.coconutketones.com


Researchers link herpes to Alzheimer's disease
Physorg.com
April 4, 2011
Laboratories at the University of New Mexico (UNM), Brown University, and House Ear Institute (HEI) have developed a new technique to observe herpes simplex virus type 1 (HSV1) infections growing inside cells. HSV1, the cause of the common cold sore, persists in a latent form inside nerve cells. Re-activation and growth of HSV1 infections contribute to cognitive decline associated with Alzheimer's disease. Details are published in the March 31 issue of PLoS ONE magazine from the Public Library of Science.
http://www.physorg.com/news/2011-04-link-herpes-alzheimer-disease.html


Herpes Simplex Virus Dances with Amyloid Precursor Protein while Exiting the Cell
Cheng S-B, Ferland P, Webster P, Bearer EL (2011)
PLoS ONE 6(3): e17966. March 31, 2011
Abstract
Herpes simplex type 1 (HSV1) replicates in epithelial cells and secondarily enters local sensory neuronal processes, traveling retrograde to the neuronal nucleus to enter latency. Upon reawakening newly synthesized viral particles travel anterograde back to the epithelial cells of the lip, causing the recurrent cold sore. HSV1 co-purifies with amyloid precursor protein (APP), a cellular transmembrane glycoprotein and receptor for anterograde transport machinery that when proteolyzed produces A-beta, the major component of senile plaques. Here we focus on transport inside epithelial cells of newly synthesized virus during its transit to the cell surface. We hypothesize that HSV1 recruits cellular APP during transport. We explore this with quantitative immuno-fluorescence, immuno-gold electron-microscopy and live cell confocal imaging. After synchronous infection most nascent VP26-GFP-labeled viral particles in the cytoplasm co-localize with APP (72.8+/−6.7%) and travel together with APP inside living cells (81.1+/−28.9%). This interaction has functional consequences: HSV1 infection decreases the average velocity of APP particles (from 1.1+/−0.2 to 0.3+/−0.1 µm/s) and results in APP mal-distribution in infected cells, while interplay with APP-particles increases the frequency (from 10% to 81% motile) and velocity (from 0.3+/−0.1 to 0.4+/−0.1 µm/s) of VP26-GFP transport. In cells infected with HSV1 lacking the viral Fc receptor, gE, an envelope glycoprotein also involved in viral axonal transport, APP-capsid interactions are preserved while the distribution and dynamics of dual-label particles differ from wild-type by both immuno-fluorescence and live imaging. Knock-down of APP with siRNA eliminates APP staining, confirming specificity. Our results indicate that most intracellular HSV1 particles undergo frequent dynamic interplay with APP in a manner that facilitates viral transport and interferes with normal APP transport and distribution. Such dynamic interactions between APP and HSV1 suggest a mechanistic basis for the observed clinical relationship between HSV1 seropositivity and risk of Alzheimer's disease.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017966
Herpes Linked to Alzheimer's Disease: 'Cold Sores' Connected to Cognitive Decline

ScienceDaily (Apr. 4, 2011) — Laboratories at the University of New Mexico (UNM), Brown University, and House Ear Institute (HEI) have developed a new technique to observe herpes simplex virus type 1 (HSV1) infections growing inside cells. HSV1, the cause of the common cold sore, persists in a latent form inside nerve cells. Re-activation and growth of HSV1 infections contribute to cognitive decline associated with Alzheimer's disease...
http://www.sciencedaily.com/releases/2011/04/110404122203.htm

Shi-Bin Cheng, Paulette Ferland, Paul Webster, Elaine L. Bearer. Herpes Simplex Virus Dances with Amyloid Precursor Protein while Exiting the Cell. PLoS ONE, 2011; 6 (3): e17966 DOI: 10.1371/journal.pone.0017966

Other things to research w.r.t. HSV-1:  Lithium

 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Home  Preface  Brain Failure  Notes  References pg. 1  References pg. 2
Nutritional Alternatives  Patricia's Protocol  Tauopathy Discussion Forum
Correspondence  Newsletters  Poems  Memory Enhancement  Curcumin  The Distillery

Click to join tauopathies

Click to join tauopathies


********************************************************************************************

Questions or comments, contact "perpetualcommotion.com" at gmail.com

Updated: August 27, 2011
Inception: August 27, 2011