Is Alzheimer's Disease Caused by Infection? (And Why It Could Matter for ME/CFS and FM)

Cort

Founder of Health Rising and Phoenix Rising
Staff member
A Post Infectious Illness?

The evidence presented here for the presence of HSV1 in the elderly human brain, for its reactivation there, its interference with cellular processes and its harmful effects on cognition,is very strong. Itzhaki

Some time ago we looked at post-infectious illnesses. From Giardia to Epstein-Barr Virus (infectious mononucleosis) to the Ebola virus we found that significant numbers of people who remain sick after an infection have been mostly been left adrift by the medical profession.

Those diseases are bad news but Alzheimer's - striking over five million people in the U.S. - a number that will only grow - is on a different level, altogether. Alzheimer's is a disease that can't be ignored; it's causing too much misery and expense for that. Recent evidence suggests, to most researchers surprise, that it could be another post-infectious illness.

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[/fright]The hypothesis suggests that even a mild infection could result in Alzheimer's. The scenario goes like this: some pathogen (a virus, bacteria or fungi) sneaks into the brain through a leaky blood-brain barrier. The immune cells in the brain surround the pathogen and block it off by building a protein wall build out of amyloid proteins. The pathogen dies and disappears - but the amyloid deposits are left behind in patients who have difficulty removing them.

Robert Moir of Harvard noticed that a similar process occurs in the body; the immune system typically immobilizes invaders by building walls around them and then attacks them. Moir asked why that process might not be happening in the brain as well. Could amyloid, he asked, have beneficial effects?

When Moir injected salmonella into the brains of mice that did not produce amyloid they died while mice able to produce amyloid plaques survived. In fact, the amyloid deposits appeared almost overnight- and at the center of each was a bacterium. That was the game-changer; the amyloid at the heart of Alzheimer’s appears to be the result of an immune reaction to a pathogen.

That's a pretty shocking finding for Alzheimer's researchers. A recent overview of the immune system's role in AD never mentioned pathogens at all.

could redefine how we understand Alzheimer’s disease. More interesting for people with ME/CFS is the fact that the pathogen at the heart of Alzheimer’s is mostly like a herpesvirus (but could also be the bacteria that causes Lyme disease, or candida or spirochetes.)

The Danger of Unaddressed Assumptions


It took a researcher who looked behind the assumption that amyloids were some sort of waste product to get to this point. Unaddressed assumptions, of course, have gotten the medical profession in deep water many times before. Consider the tragic history of radical mastectomies (RM's). From 1895 to the 1970's the gold standard for treatment of breast cancer was the radical mastectomy; a procedure in which the breast, the chest muscles around the breast and sometimes the lymph nodes were removed. Not only was the procedure disfiguring but it could leave a woman in pain for the rest of her life.

[fleft]
head-in-sand-II.jpg
[/fleft]The hypothesis behind RM's seemed to make sense. If cancer expanded exponentially from a focal point it made sense to clear out as much tissue as possible. That assumption was false, however. It turns out that cancer does not expand exponentially from a central point. When cancer's become malignant they grow in one place and then spread to different parts of the body. The massive amounts of tissue the surgeons were removing had no effect, whatsoever, in spreading the cancer.

The tragedy was that much pain could have been avoided if the medical profession had been willing to question it’s strongly held beliefs. Questions about the effectiveness of radical mastectomy were raised early by surgeons who had data showing that a less invasive technique was equally as effective. (See the Biography of Cancer").

The surgical communities resistance to employing less invasive techniques, however, meant it took decades to mount a full study. In the end it took just one large, well-designed study to prove that radical mastectomies were unnecessary. Once that happened the practice of treating breast cancer with radical mastectomies essentially disappeared; they are rarely performed anymore.

A Herpesvirus Disease?

Now it may be Alzheimer's turn. The possibility that an infection – a herpes virus infection, no less – triggers Alzheimer’s Disease is actually nothing new.

Two years ago, a clearly frustrated Dr. Ruth Itzhaki of the University of Manchester in the U.K., wrote a review article claiming that there’s a strong likelihood that herpes simplex virus contributes to Alzheimer’s.

Herpes simplex virus type 1 and Alzheimer’s disease: increasing evidence for a major role of the virus. Ruth F. Itzhaki, Frontiers in Aging Neuroscience www.frontiersin.org August 2014 | Volume 6 | Article 202 | 1

She felt that three 10-20 year-old publications had unduly influenced the field. Beliefs had hardened into dogma and once that dogma was set nothing - not even studies to the contrary - could shake it.

Positive studies, and she cites 37 of them, had not, she felt, been given their due. In fact, Itzhaki believes that the link between chronic HSV infection and Alzheimer’s is so strong that she can’t believe that there’s anything controversial about it.

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[/fright]The problem Itzahki believes is that the medical field in general resists the idea that infections play any role in chronic diseases. Itzahki believes several misconception about pathogens have contributed to the misunderstanding.
  • The first is the dogma that pathogens only cause temporary problems.
  • The second is the idea that the immune system reacts in a consistent way to pathogens. Itzaki asserts that the response to pathogens is very variable in the population; some people beat a particular pathogen off with no trouble while others can get very sick and others have middle of the road responses.
The evidence for a pathogen connection to Alzheimer's seems fairly robust. People with Alzheimer's have a higher incidence of herpesvirus infections. The blood-brain barrier - the region pathogens slip through to get to the brain - gets weakest over time at the hippocampus - the seat of memory formation - the same place plaques in Alzheimer's tend to form first. It's clear that the innate immune response in the brain accelerates greatly as we age but it hasn't been explicitly tied to pathogens.

Plus the dogma in the medical world is that the microglia and the innate immune response in the brain are part of a disease's progression - not the cause of the disease itself. It's believed that T and B-cells that gain entry to the central nervous system actually initiate the disease process. But there's no evidence that T and B-cells play a strong role in Alzheimer's; instead the innate immune system and the microglia - the two sentinels on watch for pathogens in the brain - are going gang-busters.

Years before the Harvard researchers showed that viruses cause the immune system to produce amyloid depositions in the brain, Itzaki and others showed that HSV causes amyloid products to appear. They also showed that anti-herpesvirus drugs such as valacyclovir reduced the accumulation of amyloid deposits in cell cultures.

Funding for antiviral trials in humans, however, has been denied both at the federal level and by drug companies. This is despite the fact no drugs effectively target disease progression in AD; it remains an essentially untreatable disease.

If the amyloid-infection connection wins out, though, antivirals and antibiotics could be become first-line treatments. Doctors would either find ways to remove the amyloid deposits or prevent them from being posited in the first place.

First, though, researchers have to examine be brains of Alzheimer's patients more closely to identify the pathogens they would want to target. In that they're lucky - they have lots of brain tissue to study.

There's little evidence to suggest that amyloid deposits play a role in ME/CFS or fibromyalgia. (Evidence of amyloid deposits was found Dr. Baraniuk's proteome study but that finding has not been validated.)

The role herpesviruses play in ME/CFS or FM is not clear either but the potential is there. Dr. Pridgen has found herpes simplex viruses in the gut tissues of fibromyalgia patients. A cadaver study found herpes simplex infections in the nerves of about a third of the cadavers studied. We know that HSV reactivation causes canker sores in the mouth and genital herpes and ocular herpes. In the brain it can produce encephalitis. If Itzaki is right it may even be triggering Alzheimer's.
We don’t know that herpesviruses are causing ME/CFS or FM, but if they or another pathogen end up triggering AD the impact on ME/CFS or fibromyalgia could be large.

Given AD's prevalence and cost to society efforts would surely be made to develop more effective herpesvirus drugs. It's possible that better diagnostic tests for herpesviruses could be developed as well. The role that the immune response plays in chronic illness would be highlighted as well, and post-infectious illnesses might finally start to get their due in the medical community.
 

Who Me?

Well-Known Member
The hypothesis suggests that even a mild infection could result in Alzheimer's. The scenario goes like this: some pathogen (a virus, bacteria or fungi) sneaks into the brain through leaky blood-brain barrier. The immune cells in the brain surround the pathogen and block it by building a protein wall build out of amyloid proteins. The defense is successful -the pathogen dies and disappears - but the amyloid deposits are left behind.

This process has been shown to happen in the lab and in mice and other animals but not in humans. Robert Moir of Harvard noticed that a similar process occurs in the body; the immune system walls immobilizes invaders by building walls around them and then attacks them.

The idea that amyloid was some sort of trash left behind in the brain has gone unchallenged for years. It brings to mind the idea that glial cells were just scaffolding for the neurons or that junk DNA is just junk DNA.

When Moir injected salmonella into the brains of mice that did not produce amyloid, however, they quickly died. Mice able to produce amyloid plaques survived. In fact, the amyloid appeared literally overnight. At the center of each was a bacterium.

There were indications that infections could be triggering Alzheimer's; people with Alzheimer's have a higher incidence of herpesvirus infections.

Another supportive finding is that blood-barrier gets weakest over time at the hippocampus - the seat of memory formation - which is where the plaques in Alzheimer's usually first show up.

The cause of Alzheimer's is probably not the infection, however; it's the inability of some people to clear out the amyloid plaques that form after the infection.

The next step is to use gene sequencing studies to look for microbes in brains of people who had Alzheimer's.
http://www.healthrising.org/forums/threads/are-alzheimers-and-other-neuroimmune-diseases-caused-by-infection.4409/
 

Nita

Member
Quote: "The immune cells in the brain surround the pathogen and block it by building a protein wall build out of amyloid proteins. The defense is successful -the pathogen dies and disappears - but the amyloid deposits are left behind." .... I am wondering if each time the AD patient encounters that same pathogen if even more amyloid deposits are produced without there being an active infection in the patient? If so, could something similar be happening in ME/CFS and FM. Each time we are exposed to the same pathogen that caused our disease, even though it does not trigger an active infection, our condition worsens.
 

Carollynn

Active Member
It makes me wonder about the big news last year in Alzheimer's--that taking anti-cholinergic drugs like Benadryl dramatically increases one's risk for developing dementia. It was a huge study, more than 53,000 patients. Could it be that they were taking drugs because of symptoms related to an underlying viral problem?

If the study you write about, Cort, results in further studies, I'd hope that they'd look at as many people in this other study as possible. It may be another case of virus AND, rather than virus ONLY or drug ONLY. Here's the study I"m referring to: "Use of drugs with anticholinergic properties among nursing home residents with dementia: a national analysis of Medicare beneficiaries from 2007 to 2008." http://www.ncbi.nlm.nih.gov/pubmed/25491558

It would sure be helpful to our community if there were more antivirals meds, targeted at specific viruses.
 

Katie

Active Member
Interesting theory. My dear old Dad, now passed, suffered from AD the last 3 years of his life. He had been on antibiotics several times due to contracting pneumonia x 4. But never on anti-virals.

Most elderly people have small plaques on their brain tissue with neurofibrillary tangles that mess the brain's cells and neurons. The more it increases the more damage to the brain and increased AD symptoms.

I did have a brain scan a couple years ago and I have some amyloid deposits. Whether this is due to my ME/FM or leading me down the path to AD it will take time to know. I do (or did) have HHV6 and was on anti-virals for 6 months. I did also have Epstein Barr and Giardiasis infections, plus 2 types of pneumonia-so unless these have been fully eradicated I may be in for AD in the future. However, I'm going to stay positive, the brain is always changing and neuroplasticity can occur.

If this theory is correct and antibiotics or anti-virals can stop this disease then millions of people may be prevented from going down that slow and ugly road (of AD). There are days, like today, when I have to read my sentences over and over to see what I wrote, then I stare into space for a few minutes for some unknown reason, then I look at the dog to see if he knows what I'm doing but he's older than me in dog years so he's no help at all. Now I've completely lost it!
 
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Carollynn

Active Member
Interesting theory. My dear old Dad, now passed, suffered from AD the last 3 years of his life. He had been on antibiotics several times due to contracting pneumonia x 4. But never on anti-virals.
Most elderly people have small plaques on their brain tissue with neurofibrillary tangles that mess the brain's cells and neurons. The more it increases the more damage to the brain and increased AD symptoms.
I did have a brain scan a couple years ago and I have some amyloid deposits. Whether this is due to my ME/FM or leading me down the path to AD it will take time to know. I do (or did) have HHV6 and was on anti-virals for 6 months. I did also have Epstein Barr and Giardiasis infections, plus 2 types of pneumonia-so unless these have been fully eradicated I may be in for AD in the future. However, I'm going to stay positive, the brain is always changing and neuroplasticity can occur.
If this theory is correct and antibiotics or anti-virals can stop this disease then millions of people may be prevented from going down that slow and ugly road (of AD). There are days, like today, when I have to read my sentences over and over to see what I wrote, then I stare into space for a few minutes for some unknown reason, then I look at the dog to see if he knows what I'm doing but he's older than me in dog years so he's no help at all. Now I've completely lost it!
A couple of years after I was diagnosed with ME/CFS I read about a couple of local men who had felt they were mis-diagnosed with CFS and finally accurately diagnosed with early onset Alzheimer's. Maybe there's much more overlap than we'd imagine.
 

Katie

Active Member
A couple of years after I was diagnosed with ME/CFS I read about a couple of local men who had felt they were mis-diagnosed with CFS and finally accurately diagnosed with early onset Alzheimer's. Maybe there's much more overlap than we'd imagine.
Yes, pretty scary, the over-lap makes sense, same with some other diseases. Viruses and bacterium, of any sort may affect some people forever, even after treatment. As a nurse I've seen too many patients destroyed by resistant viral and bacterial infections. A co-worker, a young woman with two little children, died after a viral infection. We were all devastated. The list goes on with other patients.
ME (and other auto-immune diseases) may have been initiated by infection and we, the ones with ME are still alive but end up suffering for years on end.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
Quote: "The immune cells in the brain surround the pathogen and block it by building a protein wall build out of amyloid proteins. The defense is successful -the pathogen dies and disappears - but the amyloid deposits are left behind." .... I am wondering if each time the AD patient encounters that same pathogen if even more amyloid deposits are produced without there being an active infection in the patient? If so, could something similar be happening in ME/CFS and FM. Each time we are exposed to the same pathogen that caused our disease, even though it does not trigger an active infection, our condition worsens.
I think that's one of the dangers of herpesviruses - that they're always there and if they get reactivated they can keep causing problems over and over again. It's interesting that stress is a know reactivator of herpesviruses - the studies indicate they can reactivated by stress even in healthy individuals - and stress makes Alzheimer's worse and certainly is problematic in ME/CFS and FM.

I think the answer is theoretically yes given the proviso that more studies in humans are needed. If a herpesvirus shows up in the brain its going to be attacked by the immune and the amyloid deposits are going to get built. People who have trouble removing those deposits are going to get hurt.

One of the treatment ideas to use herpesvirus antivirals to keep the herpesviruses down enough so that they don't make it to the brain...
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
It makes me wonder about the big news last year in Alzheimer's--that taking anti-cholinergic drugs like Benadryl dramatically increases one's risk for developing dementia. It was a huge study, more than 53,000 patients. Could it be that they were taking drugs because of symptoms related to an underlying viral problem?

If the study you write about, Cort, results in further studies, I'd hope that they'd look at as many people in this other study as possible. It may be another case of virus AND, rather than virus ONLY or drug ONLY. Here's the study I"m referring to: "Use of drugs with anticholinergic properties among nursing home residents with dementia: a national analysis of Medicare beneficiaries from 2007 to 2008." http://www.ncbi.nlm.nih.gov/pubmed/25491558

It would sure be helpful to our community if there were more antivirals meds, targeted at specific viruses.
You may have something there Carolynn. Thanks for passing that on. I imagine that any drugs that negatively impact the vagus nerve/parasmypathetic nervous system could be problematic in some people with ME/CFS/FM.

And yes, they're considering several viruses. They also know that gum disease increases the risk of Alzheimer's - so just having an inflammatory condition in the body, not the brain - somehow, I don't know if they know how - impacts what's going on in Alzheimer's. I suspect that the microglia - which feature large in AD - may be involved.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
Interesting theory. My dear old Dad, now passed, suffered from AD the last 3 years of his life. He had been on antibiotics several times due to contracting pneumonia x 4. But never on anti-virals.

Most elderly people have small plaques on their brain tissue with neurofibrillary tangles that mess the brain's cells and neurons. The more it increases the more damage to the brain and increased AD symptoms.

I did have a brain scan a couple years ago and I have some amyloid deposits. Whether this is due to my ME/FM or leading me down the path to AD it will take time to know. I do (or did) have HHV6 and was on anti-virals for 6 months. I did also have Epstein Barr and Giardiasis infections, plus 2 types of pneumonia-so unless these have been fully eradicated I may be in for AD in the future. However, I'm going to stay positive, the brain is always changing and neuroplasticity can occur.

If this theory is correct and antibiotics or anti-virals can stop this disease then millions of people may be prevented from going down that slow and ugly road (of AD). There are days, like today, when I have to read my sentences over and over to see what I wrote, then I stare into space for a few minutes for some unknown reason, then I look at the dog to see if he knows what I'm doing but he's older than me in dog years so he's no help at all. Now I've completely lost it!
I too have unsuccessfully turned to the dog at times for clarification...;)

This finding - if its validated - could have huge effects. Interest in antiviral or antibiotics would increase dramatically. I would be surprised if new, more effective drugs didn't come out to serve this huge population....There's still much to be done, apparently, to prove this hypothesis but it sounds like Alzheimer's researchers may be jumping on board. Time will tell.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
A couple of years after I was diagnosed with ME/CFS I read about a couple of local men who had felt they were mis-diagnosed with CFS and finally accurately diagnosed with early onset Alzheimer's. Maybe there's much more overlap than we'd imagine.
I see a couple of possible commonalities
  • The innate immune system seems to be over-revved in both diseases
  • Cognitive impairment is associated with both
  • Aging is associated with Alzheimer's; it's not in ME/CFS/FM but some studies suggest that aging may be accelerated in ME/CFS.
  • Herpesviruses may be implicated in all three diseases
 

GailW

New Member
I wouldn't be shocked to see it'a a virus or other pathogen. I know that when I'm at my sickest with ME, invariably a cold sore pops up on my lip - normally in winter when other viruses are making their way around.
 

Justin

Active Member
Giardia to Epstein-Barr Virus (infectious mononucleosis) to the Ebola virus we found that significant numbers of people who remain sick after an infection have been mostly been left adrift by the medical profession.
This along with mild encephalopathies stands true to me as this has been completely ignored.

All these viruses bacterias and parasites can causes a mild encephalopathy and I hope along with showcase the sequalae associated with these viruses they use better techniques to image damage in the brain and spinal cord.

This shows that we need more biological samples of tissues other than kust blood in ME/CFS.

Great article..
 

Justin

Active Member
I think Memantadine a drug for Alzhiemers that blocks the NMDA receptor is also an Antiviral.....wonder if big pharma, the governments and health authorities know more than they tell the masses
 

Gamboa

Member
Interesting and very frightening.

My father has AD and it makes me wonder if there is something genetic that we share that has allowed him to develop AD and me to have ME/CFS: an immune system defect for example.

It would be interesting to see if there is a higher incidence of AD among relatives of people with ME/CFS.
 

laureano

Member
I´ve got high igg antibody thiters both for HSV-1 and HSV-2, but I rarely experienced the "common" sympthoms of those virus in almost 20 years living with them. I wonder if they are attacking or being active in other areas of the body? if they where dormant, as the absence of common sympthoms in two decades suggest, then why the high antibody levels? I certainly have neuropaty, I´ve got tested for it... could they be causing it as this article mentions? questions and more questions. I believe that at the end, we will discover and acceptthat most chronic diseases are infectious in nature. By the way, I´ve got 2 granparents, one great grandmother and at least three great uncles wit Halzeimer
 

Stephen

Member
Let's combine two Japanese models of research and see where we get: Watanabe and Tanaka (sounds like a Japanese lounge singing act) explain the disruption to autonomic nervous system with Kondo's work that sets forth that latent herpes viruses triggers CNS dysfunction and I think we may really be on to something.

Professor Kondo has linked latent herpes virus (particularly HHV-6B) residing in the glial cells with mood disorders and chronic fatigue. He claims that this condition can effectively be treated with antiviral nasal sprays, using the olfactory nerve as a route to the brain.

Kondo says that mood disorders and chronic fatigue syndrome are likely caused by antibodies, called SITH-1, a small protein encoded by intermediate state transcript. They can induce depression in mice by injecting these proteins into them. The proteins cause upregulation of several stress hormones

Kondo and his associates have already filed a patent on their test for antibodies and for their antiviral nasal spray. He's still working on fine tuning the nasal spray and the work is not yet published. But it is very promising research, and perhaps the nasal spray treatment will be available sooner rather than later.

Kondo's work matches up nicely with Watanabe and Tanaka's work on disruption of the autonomic nervous system in the fatigue state

For further details, see this article posted on the HHV-6 Foundation Website:

http://hhv-6foundation.org/cognitive-dysfunction/can-depression-psychiatric-disorders-and-cfs-be-triggered-by-a-latent-but-neurovirulent-hhv-6b-protein
 

Stephen

Member
I would like to highlight in the article from the HHV-6 Foundation website some very interesting associations:

The article states that a number of herpes viruses use the olfactory nerve as a shortcut to the brain. A recent study mentioned in the article showed that HHV-6 could travel through the brain via the olfactory route and also found that the olfactory bulb is an important reservoir for latent HHV-6. Olfactory dysfunction also occurs in a number of neurological conditions such as myasthenia gravis, Parkinson's disease, Alzheimer's and MS.

I know Cort has blogged about potential commonality to these conditions and ME/CFS and Fibromyalgia. In myasthenia gravis muscle weakness is caused by circulating antibodies that block nicotinic acetylcholine receptors at the postsynaptic neuromuscular junction.

Acetylcholine is of much interest in ME/CFS now as Cort mentioned recent studies may link a similar immune response as that in myasthenia gravis.

Additionally, the article mentions that SITH-1 production also results in increased intracellular calcium levels, a common finding in depression and psychiatric disorders.

Even more striking is that there is a high correlation between depression and dementia with long term use of benzodiazepines. Benzodiazepines are known to increase calcium channel activity - again linked to depression, dementia and neuropathic pain!!!

Additionally, benzodiazepines (and of course all anticholinergic) to some degree or another (depending on the drug and the person taking the drug) lower a person's output of acetylcholine.

To sum up all these conditions, symptoms, and physiological actions are highly associated with latent herpes viruses residing in glial cells and the olfactory bulb. Moreover, it appears that certain drugs like benzodiazepines can also cause nervous system dysfunction and the same symptoms like depression, in part, by the same action (i.e. increased intracellular levels of calcium and downregulation of acetylcholine)

Moreover, many therapists have noticed how paced measured breathing is so helpful for depression. Proper breathing stimulates the vagus nerve and the production of, you guessed it, acetylcholine.

It seems like the research is really on to something here!!!
 

laureano

Member
The article states that a number of herpes viruses use the olfactory nerve as a shortcut to the brain. A recent study mentioned in the article showed that HHV-6 could travel through the brain via the olfactory route and also found that the olfactory bulb is an important reservoir for latent HHV-6. Olfactory dysfunction also occurs in a number of neurological conditions such as myasthenia gravis, Parkinson's disease, Alzheimer's and MS.
you know, I´ve got a quite decreased sense of smell, among the other sympthoms that are clearly from ME
 

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