It confirms Braaks hypothetical pathway, for starters, and provides a real world example of it happening. More importantly, it shows clearly the central role of the microglia and links it to alpha synuclein. We know that this virus can trigger the cascade and we suspect other viruses may be able to as well.

We also know that prenatal exposure to bacterial endotoxin (LPS) has an identical effect starting at puberty which provides a plausible explanation for YOPD. Viral origins explain later onsets.

It is very curious that the stomach wall is the point of entry. That is very rough territory bathed in stomach acid as it is. There is only one thing that can live there of all the creatures on the planet - our old friend H. pylori. Coincidence?

Finally, the microglial activation in the brain means that the area is awash in cytokines, the immune systems messenger system and inflammatory triggers. What nobody seems to link with PD is that cytokines are neuroactive! They are not inert and they interfere with normal brain function. When you feel sick with a cold and just want to lie in bed, that is not due to a toxin from the cold. It is your immune system's cytokines working on your brain to take you off your feet to conserve resources. And they can do a lot more. It isn't bacterial invaders that kill people with toxic shock, it is over reacting immune systems. If cytokines can do that to healthy people, what do you suppose can happen to PWP? Well, we know exactly what can happen thanks to our test pilot Ron and his bad tooth! That abscess triggered a flood of cytokines in his brain and Ron shut down! Once the infection cleared, the cytokines dropped and he could function again.

That means that, for each and every one of us, a certain part of our symptoms are not from damage or low dopamine or any of the usual. We are putting out cytokines every day that the microglia are active and those cytokines affect us. How much? We don't know. But if our favorite foundation is listening maybe we soon will.

Paula:

I think these folks are on the right track:

http://www.medscape.com/viewarticle/583080_11



[QUOTE=paula_w;551556]caldeerster,

is there a study on this?

Dr. Ole Isacson - Harvard

http://www.pdonlineresearch.org/resp...tial-pathology

paula

I am going to start a new thread on some possible therapies that might spin off from this research. "Microglial inhibition"

Rick,

This is all really fascinating, but I am confused. We're saying that neurodegenerative diseases like PD and Alzheimer's may start due to a viral infection entering our system through the intestines or nasal cavity? With the intestine to brain connection, I automatically think of autism as it is one of the leading theories in that disorder (I think).

In the example you cite, it would seem that the virus in and of itself can cause Parkinsonism. So do environmental toxins and/or genetics no longer play a role? Or, is the virus a singular causative for only some of us? Also, does this mean that the virus can be redressed somehow halting disease progression? These are just a few questions that come to mind...

Laura

Glad you asked that question
First, the route was predicted by a German scientist named Braak a few years ago based on Lewy bodies. This is the first time it has actually been seen to happen.

Personally, I think PD, autism, and even schizophrenia are part of a spectrum so I would not be surprised.

While it is important, to me the virus isn't the story. The real story is the inflammation and microglial activation leading to alpha-synuclein and so on. And what makes that even more important is that it is mirrored by what happens in the womb when a fetus is exposed to bacterial toxins. Several researchers have shown that that rat pup will be born with an immune system sensitized to further encounters with the toxin. That encounter will lead to the same inflammatory mess that the flu virus triggered. In short, it looks like that, as suspected, the microglial response is at the heart of PD and we have two different examples of triggers for it.

Now is when it gets more interesting and begins to explain the wide range of symptoms in individual PWP. If a virus can cause PD then it can do it at various ages, start the process, and 5, 10, 15 years later your hand starts to shake. You might be 80 years old or 40, remember nothing of the virus, and have no other risk factors.

On the other hand, you may have been born with a time bomb in your skull that eventually is activated after puberty and ticks away another 20 0r 30 years so that at 40 you notice the first symptoms. But there is a big difference between these two scenarios. The fetal toxin one leaves you open to a dozen things that can accelerate the process. I am going to paste an excert from a book I wrote a couple of years ago listing things that linked PD with this second scenario. LPS is the bacterial toxin. The links don't work but I have abstracts for each point. It all fits like a glove.




Chapter Seven
And Now the Stage is Set

The youngster looks normal enough with little sign of endocrine problems or immune systems waiting for a trigger. But within his body things are already going awry. For example, informal polling of adult PWPs revealed that fully fifty percent remembered constipation as a factor in their childhood. Cortisol can cause constipation. Systemic inflammation can cause the intestinal wall to become more permeable. In a constipated child with a leaky intestinal wall, toxins intended for elimination can be reabsorbed into the system. An ornament is added to the tree.

Those toxins can include LPS which can find its way into the bloodstream. The same inflammatory chemicals that caused the breach of the gut wall can also open the similar barrier in the brain and allow toxins such as LPS to enter and damage directly by contact or indirectly by activating the microglia.

Any hypothesis explaining PD should be able to account for the “anomalous” features of the disorder – the “weird” things that don’t make sense. The more they begin to fit into a coherent picture the stronger the hypothesis. PD has many such anomalies for us to explore and use as a gauge to evaluate this model before you. In fact, this combination of LPS, cortisol and endocrine, microglia and immune, gut and neuron, can account for more of these known facts about Parkinson’s than any other hypothesis offered to date. While the list will be somewhat long, I will provide the “facts” and their explanations in light of this model for your consideration. This is not the time for brevity but rather for testing the idea against the reality.

Fact 1- PD was little known until two hundred years ago.
Explanation - See Chapter One.

F2- Until recently, PD has been a disease of the aged.
Ex- Microglia normally become more active with age, thus increasing the age of onset of PD. <Link>

F3- Only a relatively small portion of a population develop PD.
Ex- Only a low percentage are exposed to maternal stress. Only a smaller subset of that group is also exposed to LPS. A still smaller subset is sensitized to it. And a still smaller group encounters it in their environment. And so on. Unlike an infectious process where the pool of the afflicted widens with time, this process instead narrows over time.

F4- PD appears to be increasing in incidence and affecting a younger population.
Ex- See Chapter Two.

F5- Although little acknowledged, the leading problem reported in the younger PD population is not with movement but with stress related problems.
Ex- A hyperstressed system such as described here is walking a tightrope and can collapse easily.

F6- Anti-inflammatory drugs such as NSAIDs are believed to lower the risk of PD.
Ex- Since the immune response we propose is itself an inflammatory reaction, this would be expected.

F7- Manganese exposure is believed to increase the odds of PD.
Ex- Manganese and LPS combine synergistically to damage nerve tissues. <Link>

F8- Agricultural work seems to increase the odds of developing PD.
Ex- Agricultural dust such as from seed and hay storage has an unusually high LPS content. <Link>

F9- Mercury exposure also seems causal.
Ex- Like manganese, LPS increases the neuronal damage from mercury. <Link>

F10- The “Parkinson’s Personality” is not entirely a myth and younger PWPs are particularly likely to be “responsible” sorts who occupy positions reflecting this.
Ex- Pre-natal LPS exposure produces anxiety-like behavior in the adult. One possible response to anxiety is to “take charge” in the time-honored “if you want it done right…” approach. <Link>

F11- More men than women develop PD.
Ex- Estrogen reduces the immune response to LPS exposure. <Link>

F12- Societies that consume large amounts of green tea have lower rates of PD.
Ex- EGCG, a polyphenol in green tea, strongly inhibits microglial action and inflammation. <Link>

F13- Excess levels of iron in the substantia nigra are thought to contribute to cell death and PD.
Ex- Introducing LPS into this area of the brain leads to iron accumulation there. <Link>

F14- The antibiotic minocycline is thought to be of value in treating PD.
Ex- Minocycline blocks or reduces many of the effects of LPS. <Link>

F15- The pesticide rotenone is linked to increased PD.
Ex- Rotenone and LPS combine synergistically and increase degenerative effects. <Link>

F16- Sleep disturbances in PD are extremely common.
Ex- LPS is a potent disruptor of sleeping patterns. <Link>

F17- Unexplained, generalized muscle pain is common in PD.
Ex- There are reports of similar pain resulting from LPS exposure. <Link>

F18- Milk consumption has been linked to developing PD later in life.
Ex- Milk often has a high LPS content due to the toxin’s resistance to heat and due to the fact that it is common in dairy herds. <Link>

F19- Tobacco use has been linked to reduced PD rates.
Ex- Nicotine counters the inflammatory effects of LPS. <Link>

F20- Coffee consumption has been linked to lowered PD risk.
Ex- Caffeine counters LPS inflammatory action. <Link>

Laura, a much greater definition of pd is now pretty much accepted, there is no one pd, there are multiple hit triggers; genes have been damaged by toxins, and then mutations passed on. The virus isn't new- it's long been suspected that is why teachers have a high number of pd cases - exposed to so much sickness.

anything that throws off the immune system, which then can work against us, might be a potential cause, with inflammation always being noted in pd and other illnesses. inflammation is an immune response right?

and tena, in case you are reading, i do have a reoccurring fungus that looks a little like ringworm but it isn't. it's just a circle of skin breakdown (small), and it has been reoccurring for 30? years. i don't even bother treating it, it goes away on its own. doctor says it's an immune thing.

i could go into how this all fits my belief in some fascinating biblical concepts, but don't think the forum does well on the topic. it all ties in so wel tho. maybe someday, we can all give up ownership of certain issues,[nobody owns anything really on this earth - it's just temporary. downsizing myself to only what i need in possessions was the best thing i could do. status? i blow my own relationships intentionally it seems tho i don't mean to and don't understand why] anyway no ownership of issues...obama is my president too and i don't agree with what he is doing . so let's talk and end up with real hope and no judgement. hate ruins everything..it's evil. political tension and religious tension keep us on edge and criticaL. The productive thing to do would be to attempt to understand, but it just isn't happening.

talk about deep issues that stand the test of time because they are so simple. and they involve free thinking, open mind, and purging of what is making you unhappy by just understanding each other without condemnation. this is healing......that's my point....the instructions are written down for us. so we truly are ignoring with almost stubbornness a spiritual possibiity for living with this illness with contentment till the end....even to push it back. the placebo effect is practically taunting uswith the possibilities of what we can accept if we let go of our own stubbornness to do it our own way. ok enough, i get filled with the peace it brings, not trying to offend, just sharing it. i tried not to mention names of any particular religion. just the healing that is needed for anything to work in this world right now. we are doomed with the hatred that is present now and we will score a big fat 0 in worth keeping alive

cures are not at the top of our country's empty budget and they certainly are not at the core of what drives a bio tech.

i'll save my'we are all adams and eves'story for another night ....ho ho. but i hardly own these ideas and names just get us into trouble. i think the concepts could help us all by just making us aware of what the power of a spirit of serving and caring can do for the ill.

in my world, there isn't much else.

peace,
paula

Paula,

I understand that; sorry, my post wasn't very clear in reflecting this. I simply question how our bodies make us receptive to the inflammation in the first place. Identifying another possible trigger (beyond endotoxins) in the form of a virus helps in terms of, possibly, eventually halting the disease before it really takes hold. Could we develop a vaccine, for example?

In the end, and I may be wrong, I still think we need to know what makes our brains so warm and inviting a place for PD in the first place? We all may have variable causative factors or triggers, but there has to be something we all commonly have within our brains that puts out the welcome mat to the pathology in the first place. If we look at Braak's visual model of neuronal pathology, we see that neurons either close or open the door to PD, so to speak. Braak's staging, which focuses on the olfactory region as the "birthplace" of Lewy Body Disease and PD, is wholly dependent on Lewy Bodies, but can we use this model in the absence of LBD? Some of us will, upon autopsy, have no evidence of LBD, yet we still exhibit clinical signs of Parkinsonism. How does the viral, inflammatory trigger work in the absence of the Lewy hallmark?

So many more questions arise for me. I'm a person who craves clarity; I always look at the forest instead of the tree. In adding yet another "tree", variable or pathway in the PD etiology, I feel even farther away from seeing a curative or protective treatment develop that will help the vast majority of us. What scares me is that the more I learn, the more I recognize why PD is a "boutique disease" that may in turn respond (beyond the Sinemet tourniquet) to only boutique interventions.

A couple good resources on what we've been discussing:

Parkinson's Disease: New Research (see link above for Google Book)

Olfactory system pathology as a model of Lewy neurodegenerative disease a literature review at PDOnline Research

Laura

Neuroinflammation has been just another tree for several years but this moves it into the status of "Big tree surrounded by saplings." It goes like this:
1- The St. Judes study shows, yes, that the flu virus did follow the Braak route. And it showed that, once in the brain, that an inflammatory response was mounted, microglial activation took place, alpha synuclein formed, and neurons died. Three or four trees became saplings and found a place under the big tree.
2- Having shown that inflammation and activated microglia cause the effects noted, we can look for other things that might have similar effects. At least one does - the prenatal LPS. It causes an immune response of activated microglia like in #1. So, just as #1 causes PD, so does #2. But if this is true, and it seems to be so, then a lot of trees become saplings, not because of the virus, but BECAUSE OF THE INFLAMMATION.

So, two ways of inducing PD. There may be others show up, but right now we have to - the flu virus up the nose and the prenatal immune challenge by LPS. The common element is inflammation and microglia.

However, while both #1 and #2 induce PD, they are two different forms - and this is where trees fall left and right for a moment.

#1 can strike at any age but then it needs 20 or 30 years to be noticed. This is Senior Onset and a handful of Young Onset. No bells and whisles, just some variance in the timeline.

#2, however, is something else. Within the bounds of the inflammatory response, LPS can introduce a lot of individual variety. For example, LPS amplifies the destructive power of at least some pesticides and toxins. There's a half-dozen saplings. Simalarly, LPS can amplify the toxicity of certain metals. Mercury, aluminum, manganese- all saplings now. Farm work? LPS-laden dust in the barn - sapling! Stress? Prenatal LPS disrupts the stress circuits. Etc., etc, etc.

Now, imagine mixing those two groups. They all have PD. Group #1 is fairly uniform in terms of age and backgroun.
Group #2, however, is different. As young as 20. Various backgrounds. Different speeds of progresion. Imagine what it would look like if you didn't know that there were two groups???
Wouldn't it resemble what we do see?


<<So many more questions arise for me. I'm a person who craves clarity; I always look at the forest instead of the tree. In adding yet another "tree", variable or pathway in the PD etiology, I feel even farther away from seeing a curative or protective treatment develop that will help the vast majority of us. What scares me is that the more I learn, the more I recognize why PD is a "boutique disease" that may in turn respond (beyond the Sinemet tourniquet) to only boutique interventions.»>>

Perhaps if a common denominator(s) could be located or discovered, that would open up a path for discovering substances and/or processes that disrupt the process causing PD.