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" Herpes Simplex Type I / HSV1 (oral herpes) infects the brain and

Alzheimer Herpes

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#1 hallucinogen

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Posted 07 September 2011 - 09:51 PM


" It is known by researchers today that Herpes Simplex Type I / HSV1 (oral herpes) infects the brain and is the cause of Alzheimer's. Aluminum and other elements collect in the plaques as a side effect of the inflammatory process. Aluminum is not the cause.
Furthermore, this same virus appears to be the leading cause of Type II Diabetes.
Keeping a robust immune system is key. As HSV1 patients get older, their immune systems weaken, and virus advances...leading to Type II Diabetes in some patients and Alzheimer's in others. Genetics probably contribute to the degree of susceptibility to each condition, also. It is just that simple. "
- Does anyone else know anything about this statement ? ...
Thanks in advance for more info
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#2 Lufega

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Posted 07 September 2011 - 11:00 PM

I posted a study earlier that asked whether Lysine could prevent Alzheimer's if it's really caused by herpes. Search the forum for it.

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#3 niner

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Posted 08 September 2011 - 01:35 AM

" It is known by researchers today that Herpes Simplex Type I / HSV1 (oral herpes) infects the brain and is the cause of Alzheimer's. Aluminum and other elements collect in the plaques as a side effect of the inflammatory process. Aluminum is not the cause.
Furthermore, this same virus appears to be the leading cause of Type II Diabetes.
Keeping a robust immune system is key. As HSV1 patients get older, their immune systems weaken, and virus advances...leading to Type II Diabetes in some patients and Alzheimer's in others. Genetics probably contribute to the degree of susceptibility to each condition, also. It is just that simple. "
- Does anyone else know anything about this statement ? ...
Thanks in advance for more info


It sounds like quite an overstatement, if you ask me. "Is THE cause" is crazy talk. Here is something on HSV and Alzheimers that's a little more realistic: (Free Full Text, too!)

http://www.ncbi.nlm....pubmed/20109174

Lipids Health Dis. 2010 Jan 28;9:8.
Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: a literature review.
Kuhlmann I, Minihane AM, Huebbe P, Nebel A, Rimbach G.
Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Hermann-Rodewald-Strasse 6, 24098 Kiel, Germany.

Apolipoprotein E is a polymorphic and multifunctional protein with numerous roles in lipoprotein metabolism. The three common isoforms apoE2, apoE3 and apoE4 show isoform-specific functional properties including different susceptibilities to diseases. ApoE4 is an accepted risk factor for Alzheimer's disease and cardiovascular disorders. Recently, associations between apoE4 and infectious diseases have been demonstrated. This review summarises how apoE4 may be involved in the infection incidence and associated pathologies of specific infectious diseases, namely hepatitis C, human immunodeficiency virus disease and herpes simplex.ApoE4 seems to be protective against chronic hepatitis C virus infection and retards fibrosis progression. In contrast apoE4 enhances the fusion rate of human immunodeficiency virus with target cell membranes, resulting in accelerated cell entry and faster disease progression. Its association with human immunodeficiency virus-associated dementia remains controversial. Regarding herpes simplex virus infection, apoE4 intensifies virus latency and is associated with increased oxidative damage of the central nervous system, and there is some evidence that herpes simplex virus infection in combination with the apoE4 genotype may be associated with an increased risk of Alzheimer's disease. In addition to reviewing available data from human trials, evidence derived from a variety of cell culture and animal models are considered in this review in order to provide mechanistic insights into observed association between apoE4 genotype and viral disease infection and pathology.
PMID: 20109174


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#4 MrHappy

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Posted 14 September 2011 - 04:05 AM

Don't forget Parkinson's and a whole host of other neurological disorders. Chronic relapsing herpes induced encephalitis. Look at the mechanism with l-arginine scavenging and NOS production.

I've written a lot on this topic and I'll come back and share when I'm not on my phone.

#5 MrHappy

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Posted 14 September 2011 - 10:38 PM

My feelings are that Alzheimer's and Parkinson's can be caused by the same common causes.

The symptoms will be different depending on which area of the brain is attacked first.
The striatum is the closest to the nervous system and should be first in line for virii that travel along nerve fibers (HSVx). It is also situated in a location where heavy metals can pool, owing to the influence of gravity. This gives you Parkinsonism. Parkinsonism is basically the set of symptoms experienced when the dopamine producing neurons in the striatum have been damaged or killed off, usually by Nitric Oxide Synthase.
If the virus remains latent and spreads past the striatum prior to activating, you will see symptoms defining Alzheimers or a range other neurological disorders.

I concur with the recent hypothesis that HSV-1 / 2 + APOE-4 allele, is responsible for the increased levels of NOS, causing apoptosis and the creation of protein deposits in the majority of PD and AD sufferers. This is similar in some aspects to chronic herpes encephalitis.
Parkinsonism can also be induced by chemical/heavy metal toxicity in the striatum. eg. MPTP, however HSV-1 induced Parkinsonism is more prevalent.

I base my opinion on the following:
1) Statistical correlation of HSV-1 & 2 infections to incidence of PD & AD cases
2) Oral infections of HSV-1 are in an opportunistic proximity to the brain and particularly the striatum. HSV-1 is latent in the ganglia and travels along nerve fibers, so is able to traverse the blood brain barrier easily.
3) HSV-1 is found in the protein deposits
4) NOS is produced by HSV-1 during replication, requiring L-Arginine for the process. NOS is the chemical messenger that induces apoptosis.
5) L-Arginine is synthesised directly in the brain, L-Lysine is not. Research has shown that amino acid transport efficiency across the blood brain barrier diminishes with age.
6) Reduced absorption (from dietry intake) of L-Lysine in the brain leads to an ideal environment for un-noticed replication of HSV-1.
7) The allele, APOE-4, increases the ability of latent HSV-1 to replicate in the brain. This may explain early onset diseases.
8) The a-synuclein protein has recently (August 2011) shown to be a helically folded tetramer, not unfolded as previously thought. The tangled tau proteins implicated in AD interact with a-synuclein protein implicated in PD.
9) Scavenging of L-Arginine by HSV-1 would result in less bioavailability of L-Arginine in the brain, removing the brain's normal ability to prevent aggregation of protein, resulting in the familar protein deposits.

What you can do if you suspect your neurodegenerative disease is HSV-1 based (ie. have a history of cold sores):
1000mg of acyclovir (Zovirax) + 200mg of amantadine, every day for 2 weeks, then drop to a maintenance dose of 400mg of acyclovir from then on. Expect dramatic results within a month.
Links: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Ultimately, the key to curing parkinsonism or other neurodegenerative diseases is to identify whether the cause is a pathogen or exposure to a neurotoxic substance and then treat it. The symptoms should disappear once the underlying problem is taken care of and the brain has had time to balance and repair.

I would suggest the treatment protocol should always involve testing for antibodies involving the common causes of encephalitis - HSV-1 & 2, lyme disease (from ticks - I recall reading that Michael J Fox had lyme disease once).

The majority of PD cases will revolve around HSV-1, lyme disease or basically any other pathogen that interacts with L-Arginine, stimulates or produces NOS and can pass the blood brain barrier. HSV-1 is so common amongst humans that statistically, it will be the most common cause.

If no pathogen can be identified, metal poisoning should be investigated via a hair test and neurotoxins should be tested for. The treatment will vary greatly depending on the substance.

Additionally, to help with recovery, neurogenesis (the creation of new neurons) has been observed in psychotropic substances, including many common antidepressants / MAO inhibitors / SSRIs. link

For this reason alone, replacing an existing treatment regime with a MAO inhibitor and NOS inhibitor, while identifying the underlying cause, is a far more sensible option and will prevent the usually slippery slope. The MAO inhibitor will increase the natural monoamine levels and promote neurogenesis, the NOS inhibitor will prevent apoptosis, delaying any further disease progression. This is why treatments currently in clinical trials, like Rember from TauRX and ProveBlue from ProvePharm have been so successful. These products are based on Methylene Blue, which is 1) a MAO-I 2) a NOS-I and 3) a potent antibiotic that can easily cross the blood brain barrier. link

Side note: The difficulties in researching Parkinson's Disease to-date have stemmed from 2 primary issues:
1) Most of the research has been conducted on mice with induced Parkinsonism (created by neurotoxic substances), which means the focus has been on treating the symptoms, rather than identifying the origins.
2) Until August this year, the a-synuclein protein models being used were incorrect, owing to the extraction technique and processing. Expect to see more correlation with Alzheimer's Disease following this. link
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#6 golgi1

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Posted 20 September 2011 - 11:06 PM

Great post Mr Happy. I'll make a list for everyone who might read your advice. Please add to it or correct it as necessary:

Natural NOS inhibitors are:
Pycnogenol / Proancyanidins
Silymarin
Others Flavanoids?

OTC/Available MAOI-Bs include:
Selegiline (irreversible)
Rasagiline (irreversible)
Rhodiola (reversable)

MAOI-As include:
Reseravtrol
Curcumin
Piperine
Harmal
Rhodiola
Prescription Solutions

Would prolonged NOS inhibition with something like large doses of pycnogenol, whilst simultaneously avoiding supplemental arginine, have a deleterious effect on endothelial function over a long period of time? I wonder. Or, perhaps, endothelial function would normalize and the body would make efficient use of whatever arginine is available in the brain, regardless.

Edited by golgi1, 20 September 2011 - 11:24 PM.


#7 MrHappy

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Posted 23 September 2011 - 02:30 PM

The problem is that the lysine/arginine balance is delicate. While arginine is required for HSV-1 to replicate (and cause neuron death as an unfortunate byproduct), the brain also needs it for preventing the protein deposits, as well as promoting general vascular health, etc.

Taking a NOS-I at high doses for an extended period of time also can lead to the inability of the body to induce apoptosis when it actually is required eg. Killing cancerous cells.

Your best bet is to use the NOS-I as a stall and attack the virus head on with an antiviral. Valacyclovir @ 1000mg + amantadine @ 200mg per day for 2 weeks, then move to a maintenance dose of 400mg valacyclovir, daily. Should see results in a month.

Looking forward to bavituximab being released for public usage. This kills HSV dead. Not just active cells, latent cells too! It works by binding to an exposed lipid on the outside of an infected cell, causing the immune system to kill off that cell. Stunning design!

#8 robosapiens

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Posted 26 September 2011 - 08:12 PM

One could use BHT for similar purposes, if one is so inclined

#9 MrHappy

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Posted 26 September 2011 - 09:43 PM

Brilliant!! Hadn't come across that one.

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#10 niner

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Posted 27 September 2011 - 01:00 PM

The symptoms will be different depending on which area of the brain is attacked first.
The striatum is the closest to the nervous system and should be first in line for virii that travel along nerve fibers (HSVx). It is also situated in a location where heavy metals can pool, owing to the influence of gravity. This gives you Parkinsonism. Parkinsonism is basically the set of symptoms experienced when the dopamine producing neurons in the striatum have been damaged or killed off, usually by Nitric Oxide Synthase.
If the virus remains latent and spreads past the striatum prior to activating, you will see symptoms defining Alzheimers or a range other neurological disorders.

Thanks for an interesting post, MrHappy. I think there probably is something to the HSV hypothesis. I have one correction to make, and an observation: The effect of terrestrial gravity on metals or any small molecule is vastly smaller than thermal energies at body temperature, so there wouldn't be any pooling going on. If the striatum is first in line for virii traveling along nerve fibers, it would stand to reason that the rate of PD would be higher than the rate of AD, but isn't it the other way around?

#11 MrHappy

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Posted 28 September 2011 - 06:37 AM

Yes, however it really depends on a number of factors - where any existing proteins are located and of course how perforated the blood brain barrier is. The APoE-4 allele contributes to the BBB condition. So, as usual genetic expression has a major role in disease progression. HSV normally stays hidden/latent in neurons and ganglia and becomes active in proteins. The double-kicker is that since L-Arginine is used to remove the protein deposits, there is considerably more fuel available for active-state replication.

#12 Ark

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Posted 15 November 2011 - 07:47 AM

Great post Mr Happy. I'll make a list for everyone who might read your advice. Please add to it or correct it as necessary:

Natural NOS inhibitors are:
Pycnogenol / Proancyanidins
Silymarin
Others Flavanoids?

OTC/Available MAOI-Bs include:
Selegiline (irreversible)
Rasagiline (irreversible)
Rhodiola (reversable)

MAOI-As include:
Reseravtrol
Curcumin
Piperine
Harmal
Rhodiola
Prescription Solutions

Would prolonged NOS inhibition with something like large doses of pycnogenol, whilst simultaneously avoiding supplemental arginine, have a deleterious effect on endothelial function over a long period of time? I wonder. Or, perhaps, endothelial function would normalize and the body would make efficient use of whatever arginine is available in the brain, regardless.



What about Naridal>It's MAOI-B

#13 MrHappy

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Posted 20 November 2011 - 12:55 PM

Thought I'd drop back here with an update. For anyone reading this looking to treat alzheimer's, the damage can be reversed. :)

Lots of info in the uridine thread:
http://www.longecity...ne-uridine-dha/

For anyone trying to banish hsv-1/2 - while you're waiting for bavituximab - check out butylated hydroxytoluene (BHT).
http://www.advance-health.com/bht.html

Start at 250mg and scale up slowly to 1250-1500mg.. Anecdotal evidence (no formal clinical trials) has mentioned people testing negative for hsv antibodies after 3+ months of dosing BHT.

#14 mikeinnaples

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Posted 21 November 2011 - 03:18 PM

The emotional impact of discovering that you have herpes can outweigh the physical health issues one has to deal with. Go to SingleHerpes.com to find support and other singles with herpes in your area!


Umm ...LOL?

You do realize that most of the world's population has HSV1 right?

#15 gamesguru

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Posted 21 November 2011 - 03:41 PM

Umm ...LOL?

You do realize that most of the world's population has HSV1 right?

Most people have it, but some people don't have an immunity which can ward it off.

#16 GhostBuster

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Posted 22 November 2011 - 02:30 PM

There's an interesting thread under the category "aging theories" that gives to this theory of virus infection theory a nice point of reference. An idea that many major diseases are caused by pathogens makes a lot more sense that overly ideological view of good/bad genes behind human health and sickness.

http://www.longecity...cause-of-aging/
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#17 Denjin

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Posted 28 November 2011 - 09:09 PM

Haven't they found a genetic link to Alzheimer's? At least in that if your immediate relatives have it the chance of you getting it is a lot higher? I'm very doubtful of these claims.
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#18 niner

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Posted 28 November 2011 - 09:50 PM

" It is known by researchers today that Herpes Simplex Type I / HSV1 (oral herpes) infects the brain and is the cause of Alzheimer's. Aluminum and other elements collect in the plaques as a side effect of the inflammatory process. Aluminum is not the cause.
Furthermore, this same virus appears to be the leading cause of Type II Diabetes.
Keeping a robust immune system is key. As HSV1 patients get older, their immune systems weaken, and virus advances...leading to Type II Diabetes in some patients and Alzheimer's in others. Genetics probably contribute to the degree of susceptibility to each condition, also. It is just that simple. "
- Does anyone else know anything about this statement ? ...
Thanks in advance for more info

If it were true that aluminum was not causal, then how would an increase in aluminum exposure substantially raise one's risk of Alzheimer's? There is some pretty good epidemiology on that. I think this statement, whatever the source of it, is veering into tinfoil hat territory. And HSV is "the leading" cause of T2D? Please. This is straight outta nutville.

#19 Delafuente

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Posted 01 December 2011 - 06:15 AM

Are there any reputable online sources that supply amantadine and acyclovir? International Anti Aging Systems doesn't seem to offer either.

#20 Delafuente

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Posted 01 December 2011 - 09:39 PM

Or any sources for BHT? I expected to find some at the vitamin shoppe, but they don't have any. Any reputable online sources? It's apparently a supplement so it should be easier to obtain than amantadine and acyclovir.

#21 MrHappy

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Posted 03 December 2011 - 10:43 AM

Plenty of sources. You can buy Vitamin Research Products 60 x 350mg caps for around $13 + shipping, carefully sold as a 'food preservative / anti-oxidant'.

You can also buy 1 pound of pure BHT for about $35 in bulk.

#22 Delafuente

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Posted 16 December 2011 - 08:36 PM

I ended up buying LEF's BHT. Currently taking 850 mg/day. Somewhat concerned about potential liver toxicity I've heard about.
I wonder what the pros/cons are between BHT and valacyclovir.

#23 Mind

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Posted 16 December 2011 - 08:55 PM

Where the heck did the original statement in the first post come from? Let us see the studies. Most of the world's population has Herpes1. If it was the primary cause of AD and PD, you would think the link would be substantially proven many times over by now. All it would take are simple population studies.

I am not going to rule out infectious disease having some affect on age related diseases, but they ARE AGE-RELATED diseases (AD, diabetes, and cancer, anyway). The rationale and data for the damage (SENS) theory of these diseases is much stronger IMO.

#24 seivtcho

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Posted 25 December 2011 - 07:59 AM

I want also to ask 3 more questions to those asked by Mind.

First, can this be called "Herpes Simplex Type I aging theory" If so, to add it in the aging theories list.

Second are there studies, comparing the percentages of the people, who have HSV1 and developed AD versus the percentage of people, who have HSV1 and did NOT develope AD.

Third, are ther studies, that compare the percentage of people, who have HSV1 and developed PD versus the percentage of people, who have HSV1 and did NOT develope PD.

#25 MrHappy

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Posted 25 December 2011 - 09:18 AM

http://www.news-medi...rs-disease.aspx



#26 saxiephon

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Posted 15 February 2012 - 04:53 PM

MrHappy,

What do you think about daily dosing of allicin for HSV1?

Planta Med. 1992 Oct;58(5):417-23.
In vitro virucidal effects of Allium sativum (garlic) extract and compounds.

Weber ND, Andersen DO, North JA, Murray BK, Lawson LD, Hughes BG.

Source

Department of Microbiology, Brigham Young University, Provo, Utah 84602.

Abstract

Garlic (Allium sativum) has been shown to have antiviral activity, but the compounds responsible have not been identified. Using direct pre-infection incubation assays, we determined the in vitro virucidal effects of fresh garlic extract, its polar fraction, and the following garlic associated compounds: diallyl thiosulfinate (allicin), allyl methyl thiosulfinate, methyl allyl thiosulfinate, ajoene, alliin, deoxyalliin, diallyl disulfide, and diallyl trisulfide. Activity was determined against selected viruses including, herpes simplex virus type 1, herpes simplex virus type 2, parainfluenza virus type 3, vaccinia virus, vesicular stomatitis virus, and human rhinovirus type 2. The order for virucidal activity generally was: ajoene > allicin > allyl methyl thiosulfinate > methyl allyl thiosulfinate. Ajoene was found in oil-macerates of garlic but not in fresh garlic extracts. No activity was found for the garlic polar fraction, alliin, deoxyalliin, diallyl disulfide, or diallyl trisulfide. Fresh garlic extract, in which thiosulfinates appeared to be the active components, was virucidal to each virus tested. The predominant thiosulfinate in fresh garlic extract was allicin. Lack of reduction in yields of infectious virus indicated undetectable levels of intracellular antiviral activity for either allicin or fresh garlic extract. Furthermore, concentrations that were virucidal were also toxic to HeLa and Vero cells. Virucidal assay results were not influenced by cytotoxicity since the compounds were diluted below toxic levels prior to assaying for infectious virus. These results indicate that virucidal activity and cytotoxicity may have depended upon the viral envelope and cell membrane, respectively. However, activity against non-enveloped virus may have been due to inhibition of viral adsorption or penetration

#27 saxiephon

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Posted 15 February 2012 - 05:01 PM

Also you may want to review the many potential benefits of allicin on this site:
http://flipper.diff....items/info/1886

#28 saxiephon

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Posted 15 February 2012 - 06:18 PM

Here are a couple discussions that support MrHappy's hypothesis:

http://www.life-enha...ate.asp?id=2437

http://www.scienceda...10404122203.htm

#29 saxiephon

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Posted 16 February 2012 - 05:54 PM

Here's a Great Article for this thread:


Is Herpes A Trigger for Alzheimer’s Disease?


By Erik Goldman - Vol. 12, No. 2. Summer, 2011


Posted Image

Transmission electron micrograph of Herpes Simplex Virus. Herpes DNA has been isolated from Amyloid plaques in the brains of people with Alzheimer's disease. A number of recent studies are pointing to herpes, and possibily other infectious pathogens as triggers for deposition of amyloid. Image courtesy of Pasieka/Science Photo Library


BELLEVUE, WA ⎯ An emerging line of research is implicating the herpes simplex virus as an underlying trigger for formation of β-amyloid plaques in the brain, the hallmark of Alzheimer's disease.
A number of recent studies—along with the failure last summer of a highly touted anti-amyloid drug--are pushing Alzheimer's researchers and clinicians alike to rethink the role of β-amyloid in the etiology of this disorder.
The emerging paradigm suggests that β-amyloid, far from being a malevolent biochemical culprit, is an endogenous antimicrobial protein that the brain secretes in self-defense against infectious pathogens, said David Perlmutter, MD, at the Institute for Functional Medicine's 20th annual symposium.
The notion that there may be an infectious component in the etiology of Alzheimer's disease—and herpes is not the only suspect--opens up new possibilities for preventing and treating this devastating condition.
β-Amyloid: Friend, Not Foe
"It may not be such a good idea to try to get rid of β-amyloid," said Dr. Perlmutter, challenging the prevailing wisdom that β-amyloid deposition is a fundamentally pathologic process. While buildup of amyloid plaque clearly correlates with neurodegeneration and disease progression, amyloid secretion is actually a primitive self-defense mechanism gone awry. Use of anti-amyloid therapies, like Lilly's now-defunct Semagacestat, is akin to treating the smoke while ignoring the fire.
"β-amyloid may actually be a friend, not a foe," said Dr. Perlmutter, a neurologist & functional medicine physician in Naples, FL, who is author of The Better Brain Book, and Power Up Your Brain.
"β-amyloid is, essentially, a host-defense peptide," one of a number of Antimicrobial Peptides (AMPs) secreted within the brain. Stephanie Soscia and colleagues at the Mass General Institute for Neurodegenerative Disease recently showed that β-amyloid has marked microbicidal activity against several human pathogens, including Candida albicans, Escherichia coli, Staphylococcus aureus and pneumoniae.
In their seminal 2010 paper, the authors assert that, "a reevaluation of the role of β-amyloid may now be warranted in view of these data suggesting that the peptide functions as an AMP in tissues. Rather than β-amyloid acting as a sole independent initiator of neuroinflammation, our data raise the possibility that the peptide may be part of a response mounted by the innate immune system." They add that, "an absence of the peptide may result in increased vulnerability to infection." (Soscia SJ et al. PLoS One. 2010;5(3):e9505.)
Combs & colleagues at the Alzheimer's Research Laboratory, Case Western Reserve University showed that β-amyloid is a key factor in triggering secretion of inflammatory cytokines from the microglial cells among the fibrillary tangles characteristic of Alzheimer's disease. This cytokine release can be quelled by several different anti-inflammatory drugs (Combs C, et al. J Neurosci. 2000; 20(2): 558-67).
(For more on Amyloid and Alzheimer's, read: Angelica Extract Brings New Mechanism to Bear on Alzheimer's Disease by Dr. Thomas Walshe).
An Inflammatory Disease
As it is in cardiovascular disease, systemic inflammation is turning out to be a key factor in Alzheimer's. Holmes and colleagues, at the Division of Clinical Neurosciences, University of Southampton, UK, studied cognitive function in 300 people with mild to severe Alzheimer's disease, comparing the cognitive scores against circulating TNF-α levels, an indicator of systemic inflammation.
Roughly half of the subjects had systemic inflammatory events, including respiratory, genitourinary and gastrointestinal infections associated with an increase in serum TNF-α. Elevation of this cytokine correlated with a doubling in the rate of cognitive decline over a 6-month period (Holmes C, et al. Neurology. 2009; 73(10): 768-74). High baseline TNF-α was associated with a 4-fold increase in the rate of cognitive decline. Subjects with the lowest TNF-α levels throughout the study showed no cognitive decline over the 6-month period.
Clearly β-amyloid is central in the inflammatory process of Alzheimer's disease. For the last 2 decades, pharmaceutical developers have viewed it as a prime cause—and therefore a prime therapeutic target. Echoing the cholesterol hypothesis of heart disease, the prevailing logic on Alzheimer's is that if β-amyloid is characteristic of the disease, and its buildup correlates with cognitive impairment, then amyloid reduction will prevent or delay dementia.
That's not how it is turning out, Dr. Perlmutter said. Last August, the Eli Lilly Company shelved its Semagacestat, an anti-amyloid drug that was leading the race to be the first pharmaceutical therapy for Alzheimer's.
In the IDENTITY (Interrupting Alzheimer's dementia by evaluating treatment of amyloid pathology) trial, a Phase III study involving more than 3,000 Alzheimer's patients, those treated with the drug had more rapid progression and worsening of symptoms compared with those on placebo. The trial was aborted before completion.
The HSV Connection
If, as Dr. Soscia's group at Mass General contends, β-amyloid is an antimicrobial defense peptide, then two big question emerge: What pathogen(s) trigger it's secretion? And, Why are some peoples' brains vulnerable while others are not?
There is some compelling recent evidence pointing to herpes simplex virus type 1 (HSV1). This virus is highly prevalent, affecting roughly 90% of all adults, a necessary criterion for an infectious etiology in a disease like Alzheimer's. It can also remain latent throughout someone's life, and can reactivate in the peripheral and possibly the central nervous system later in life.
In a 14-year study of 512 elderly people with no signs of dementia at baseline, Luc Letenneur and colleagues at the INSERM, Bordeaux, France, showed a marked correlation between the presence of anti-HSV IgG and IgM and the risk of developing Alzheimer's disease. Presence of anti-HSV IgM conferred a 2.55 hazard ratio for Alzheimer's, and was a bigger risk factor than presence of the APOE-4 allele, the so-called "Alzheimer's gene."
"This is a very robust risk factor for Alzheimer's," Dr. Perlmutter commented.
The Letenneur group found that reactivation of HSV seropositivity is highly correlated with incident Alzheimer's, and may contribute to neurodegeneration. "Recurrent reactivation of HSV might act as a potent stimulus to the brain microglia, increasing the level of cytokines and initiating a positive feedback cycle that gives rise to an increasing accumulation of pathological changes (Letenneur L, et al. PLoS One. 2008; 3(11):e3637)."
In a seminal 2008 paper, researchers at the University of Manchester, UK, showed that HSV1 DNA is present in tissue from the frontal and temporal cortices—key brain regions affected by Alzheimer's—in a high proportion of elderly people (Itzhaki R, et al. J Alzheimers Dis. 2008 May;13(4):393-405). Interestingly, viral DNA was not found in the occipital brain regions, which are not affected by Alzheimer's disease.
The Manchester group, led by Dr. Ruth Itzhaki also isolated antibodies to HSV1 from cerebrospinal fluid in elderly people with and without Alzheimer's, but not from a cohort of younger people, suggesting that the process by which herpes enters the central nervous system is a slow, life-long one.
Most recently, Itzhaki's team showed that HSV1 DNA could be identified in amyloid plaque samples from people with symptomatic Alzheimer's disease, as well as from asymptomatic individuals. Among those with Alzheimer's, 72% of the viral DNA was plaque-associated. "Localization within amyloid plaques reflects a specific association, not a background random distribution," the authors note. "These results support the deduction that HSV1 is a major cause of plaque formation." (Wozniak MA, et al. J Pathol. 2009;217(1):131-8).
Dr. Itzhaki contends that HSV is "a significant etiological factor in Alzheimer's disease," and has gone as far as suggesting the use of antiviral agents to treat or even to prevent Alzheimer's.
The idea that herpes might play a role in Alzheimer's is not new. In 1982, Melvyn J. Ball, a neuropathologist at Oregon State University, noted that HSV1 could establish a lifelong presence in the trigeminal nucleus, which has projections into the mesial temporal areas of the brain, commonly affected in Alzheimer's disease. Dr. Ball proposed that reactivated HSV1 in the trigeminal nucleus could migrate "downstream" to appear as herpes labialis ("cold sores"), or "upstream" into limbic areas of the brain, leading to dementia.
Gene-Pathogen Interactions
A majority of adults carry HSV. Yet, only a small proportion ever develops Alzheimer's. Doesn't that obviate the possibility that the virus is causative?
It's not quite so simple, explained Dr. Perlmutter. Like most other chronic diseases, Alzheimer's is multifactorial. Infections like HSV may be triggers, but they are not the only factors. Genes like APOE-4 play a role, but neither do they give a complete explanation of the pathology.
"We're talking about environmental contagion interacting with genetic factors, and playing out differently in different people," he said. The available evidence suggests that HSV1 and the APOE-4 allele are cofactors.
Relatively few people who carry HSV1 also carry the APOE-4 allele, but those who do are consistently at greater risk for outbreaks of herpes cold sores. Presence of the APOE-4 allele also increases risk of HSV1 spread to the brain, as has been shown in rodent studies. Dr. Itzhaki's group in Manchester has proposed that reactivation of HSV in the brains of APOE-4 carriers results something akin to a mild, localized encephalitis resulting in direct neural damage, and triggering chronic inflammation that lead to further damage over time.
The interactions between HSV and APOE-4 was the subject of an excellent review article by Urosevic and colleagues in the Journal of Alzheimer's Disease (Urosevic N, Martins RN. J Alzheimers Dis. 2008 May;13(4):421-35).
HSV is not the only infectious pathogen that has been linked with Alzheimer's disease, said Dr. Perlmutter. Chlamydia has also been implicated. Wayne State University researchers found DNA from Chlamydophila (Chlamydia) pneumoniae brain tissue samples from 20 of 27 Alzheimer's patients (74%), but only 3 of 27 controls (11%) (Gerard HC, et al. FEMS Immunol Med Microbiol. 2006 Dec; 48(3): 355-66).
The investigators were able to culture Chlamydia from some of the brain tissue samples, indicating that the organisms were viable and metabolically active. Astrocytes, microglial cells, and neurons all ably served as hosts for C. pneumoniae, and infected cells were closely associated with neuritic senile plaques and neurofibrillary tangles.
Treatment Implications
If infections like HSV and Chlamydia play a role in Alzheimer's disease, then strategies aimed at preventing and controlling these pathogens might prevent the dementia.
"When we see herpes cold sores on the lips or faces of our elderly patients, we need to ask what's going on in their brains," Dr. Perlmutter said. Though there are not yet any studies confirming that anti-herpes therapies---natural or pharmaceutical—can prevent or slow Alzheimer's, there's little harm in trying. Dr. Perlmutter believes antivirals and lysine supplementation should be used routinely.
HSV1 requires the amino acid, arginine, for replication. Viral replication is suppressed in microenvironments rich in lysine but poor in arginine (lysine competes with arginine). There are 7 double blind, placebo-controlled studies of lysine supplementation, at doses of 500-3,000 mg per day, for preventing herpes labialis outbreaks. Six studies found lysine to be effective. These studies are reviewed in a paper published last year by Dr. Robert Rubey (Rubey R. Neuropsychiatr Dis Treat. 2010; 6: 707–710).
Though there are not yet any intervention trials showing that lysine can reduce risk of Alzheimer's, population studies suggest that diets high in lysine and low in arginine are associated with lower rates. Foods rich in lysine but low in arginine include whole grains, fruits, vegetables, cheese, yoghurt and fish. People at risk for Alzheimer's (and herpes labialis for that matter) should increase their intake of these foods. On the other hand, tofu and other soy foods have relatively high arginine to lysine ratios, and should probably be avoided or minimized.
According to Dr. Perlmutter, lysine supplementation poses negligible risk but tremendous potential benefit for prevention or attenuation of Alzheimer's. He added that Vitamin D also has a role. Among its myriad health benefits, Vitamin D activates cathelicidin, another endogenous antimicrobial peptide secreted by the brain in response to pathogens. Several population studies over the last 2 years have shown a connection between low serum vitamin D and increased risk of Alzheimer's disease and other forms of cognitive impairment.
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#30 MrHappy

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Posted 17 February 2012 - 10:20 PM

That's some good reading. :)

You might like this thread:
http://www.longecity...erpes-activity/






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