Alzheimer's Disease and serpins

When I was trying to decided if gluten, casein, and ovalbmin were functioning as serpins, serine protease inhibitors, I looked at all serpins.

 I had wanted to show that Candida could cause autoimmune disease by switching between a yeast and a mold state.  The notion of root halting came from a golf course grass experiment at Ohio state.  That corn gluten halted not just grass seed from sprouting roots but had blocked a parasitic mold from creating hyphals. I wanted to know if gluten, casein, and ovalbumin halted root growth.

I started to look at serpins as off growth switches thus i pondered if serine proteases were on root growth switches.

  I looked at the maspin of breast cancer which when lost caused out of control cellular growth. In breast cancer there are several  "on" switch proteases.


I looked at neuroserpin. Did it halt the growth of nerves? I did not find an answer. I did not find a specific target protease.  What I did find was APP.  When clipped it became the notorious amyloid plaques but the normal function of the regular protein was unknown.  APP was a serine protease so could it be an on growth switch?

I suddenly viewed Alzheimer's differently.  Everyone views it as a state of brain cell death but what if the brain cell was actually trapped in a state of growth first?  Were the nerve axons growing like roots?

Early onset Alzheimer's disease is common in the mother's of downs syndrome children. This seemed to indicate a mitochondria problem.  We have, the good, the bad and the ugly mitochondrias and perhaps the ugly ones are involved in Alzheimer's. We know that some of these mother's have mitochondria that do not function well because they passed on poor functioning mitochondria to their children.

 During normal synaptogenesis  the mitochondria move to the axon tips of the neurons. Axon growth would not be possible if the mitochondria do not make it there to supply the energy.  When the mitochondria of Alzheimer's disease mouse models were recently illuminated the mitochondria were not reaching the synapse.  Is early Alzheimer's a failure of the mitochondria to support growth?

Late onset Alzheimer's involves the apoE  genotype which means the lipid supplier, the one that carries the lipid wall building supplies to the nerve becomes important. Most people have apoE3 but those with late stage Alzheimer's have apoe4.  We know as we age our dietary absorption decreases and with the growth already choking with a bad apoE4 delivery man perhaps nerve growth is slowly dwindles?  The use of statin drugs have been said to cause a memory dysfunctional state in patients perhaps by limiting the lipids.  So far this could make sense, in order for a nerve to grow it needs supplies.

So how does APP fit in and end up as plaques in both cases?

Is APP a growth on switch? Studies have been done in mice which show that in young mice with app knocked out seem fine but  the older mice that seem to have issue. Consider that young mice or even kids have a rapid state of nerve growth and pruning whereas adults have a slower state of growth and not so much pruning.  Perhaps app is the growth switch of the adults?  The app knock out mice did  have sparse spinal nerves compared to normal mice. When does the production of APP actually start? when we become adults? Is that why this is a disease of adults?

How do all the theories converge to explain the app becoming cleaved and becoming the amyloid plaques we find in Alzheimer's patients? What could actually be happening? Nerve growth factor induces the expression of app.  App then creates a growth state which can be shut off by neuroserpin.  If something goes wrong with the state of growth would the nerve attempt to make more of the "on switch" which is app? does the nerve says it needs to grow and keeps sending the app growth switch but the lack of supplies or the lack of energy cause the app to be broken down instead? Could it be that amyloid plaques are a result of stunted growth not a cause of the nerve failure?

That Alzheimer's is not so much a disease of cell death but a failure of cell growth?

Okay i have drifted off topic, but this is a blog and i am allowed to do that.  I will end with an interesting thought about mitochondria moving.  In fireflies the off and on glow is controlled very quickly by NO acting on their mitochondria.  Wouldn't it be neat if the mitochondria can control their own locomotion with their own NO synthase?  ahhh I think too much some days.  

Other thoughts:
There are things that can enhance memory which one could look at as greasing the gears of the mitochondria. Vitamin E and omega fats are not just the insulation of cells but they are the main ingredient of the inner mitochondria membrane.  Vitamin E does not just protect the omega fats from oxidation but stabilizes the membrane instead of cholesterol, something that i think is currently over looked in the field. That omega fats require vitE to work. Low levels of vit E are associated with poorer memory as we age.

Parkinson's has currently been viewed as a mitochondria disease in that PURL has been indicated.  Purl is a rhomboid protease involved in the morphology of mitochondria.  This would not stop the functioning of the mitochondria rather make transport of them down the axon more difficult.  Purl might be breaking a large mitochondria suv into smaller mitochondria coopers....so to speak...thus a sporatic energy supply.  I don't know if any one has looked into that but it makes me wonder.  If Resveratrol is now said to induce mitochondria biogenesis and has been shown to extend the lifespan of yeast and flies....could it counter the problem in Parkinson's somewhat?


I hope this inspires people out there to think...literally...may Alzheimer's be a fixable state of growth error?

Thanks for listening,
Angela Biggs

autoimmune celiac disease trigger hypothesis

2016: This hypothesis was wrong about the morphology switching.  Eventually I looked at the list of gluten sensitive infections and some were not dimorphic. All the linked infections were known to cross the intestinal barrier: e.coli, sutterella, t.gondii.....which lead to a split in the hypothesis.  Gluten and casein were not required to build up to autoimmunity but could inflame the situation. See the newer posts.


Celiac disease

I just recently found this ancient article which seems to support the notion that e.coli is involved with Celiac disease.
http://www.ncbi.nlm.nih.gov/pubmed/1107934

When I started researching only Celiac disease was gluten triggered.  Then when my son was born I read in a Parents magazine how an autisic child appeared to be gluten and casein sensitive and that removal of these proteins reversed his condition.  I started to wonder if Autism was autoimmune like Celiac disease.

I researched online and discovered that schizophrenia too had been associated with gluten and casein...so i had 3 very different diseases with a strange overlap.

Then my daughter developed eczema.  We have no family eczema. The neighbors' kids had eczema.  I felt sort of crazy telling the doctors that I believed she caught this because we didn't have this allergy.  I noticed the eczema waxed and waned with milk and egg.   I started to think that what ever this infection was it was changing with milk or egg.

Then on a fluke I read an article on organic weed killers which made me consider gluten as a switch on an infection like what I was seeing on with the eczema.

Corn gluten halts crab grass seeds from forming roots. When you look up the original Ohio state research you discover the original experiment was about a parasitic grass mold.  Seems that not only did grass seed not sprout roots but the mold failed to be thrive and be parasitic on the golf-course grass they were protecting.   

My thoughts: gluten prevents root growth and mold hyphals are like roots! Gluten was stopping a morphology switch.  The fungus could not exist as a mold and had to become a yeast.  suddenly i thought of beer yeast...running out of sugar and changing morphology and falling to the bottom of the glass..realizing that lots of fungal infections must do this.

So my first focus was that these autoimmune diseases must be fungal induced. Made sense...I had studied type 1 diabetes and some were associated with candida.

I found an Italian paper where gluten induced antibodies in celiac patients. I realized because I had done diabetes research that celiac disease if they, pateints,  didn't have gluten they were protected from type 1 diabetes.  Perhaps the immune system only sees one morphology and reacts to and produces antibodies to it? Gluten and casein were causing a peek-a-boo effect.

I started looking for infections in Celiac disease. I could not find fungal infections. The only correlation I could find was a history of bladder infections in a lot of the patients.  I looked at the e.coli that was involved in bladder infections. Unlike most e.coli which causes food poisoning the bladder infection form was dimorphic!  That e.coli had 2 morphologies a rod and a thread like form.  The enzyme controlling it was called LON meaning long.  This enzyme was already known to be casein controlled.  Even more exciting, the e.coli was shown to change morphology with hydrocase (which contains casein).  

If gluten is so similar.....does it act on LON too? Does E.coli change morphologies even faster with gluten? It would help explain celiac disease if it were true.

This is where we are and what needs to be tested by someone out there.

E.coli fits the celiac disease puzzle well because it can explain the over lap of celiac and autoimmune liver disease and type 1 diabetes.  E.coli makes bilirubin when it breaks down red blood cells which...our liver makes bilirubin.  E.coli makes insulin-related material that the bioassay for insulin reacts with.

The last step in my theory has to do with what pushes the immune system from a state of high antibodies to autoimmune attack: viruses.

Viruses must cause cross-targeting.  For Celiac disease any virus that would infect the intestine...for liver disease hepatits...for the pancreas the flu virus infects it.

This is just a hypothesis. This is not proven but something to consider, to test.....it makes logical sense.

2016 update: gluten sensitivity does not have to do with dimorphic switching rather appears when an infection that can tear through the intestinal barrier is there. Gluten then crosses and ramps up the immune system.  Gluten and celiac occur when autoimmune cross-targeting occurs at the intestine ontop of the infections making a hole.  Please see newer posts.

Can anyone see or understand what I saying?
Hopeful,
Angela Biggs

Update on the theory:

 I have the most figured  out for celiac disease.  I have been dragging my feet about posting what I know only because I was hoping to find the last piece of the puzzle first.  I don't have the gluten piece, the most critical piece and the last piece i need.

Celiac disease has been associated with a history of bladder infections.  The most common cause of bladder infections is a form of e.coli that is dimorphic in that it shifts between a rod morphology and a long filament morphology.

The enzyme responsible for the long morphology is called LON (long with the g dropped off). LON is a serine protease. Casein is not just a substrate but a stimulator of the LON enzyme.

The action of casein on LON could explain why hycase solutions which contains casein causes e. coli to change morphology.  (not all e.coli just some varients)

This leads me to ponder does gluten which is similar in structure to the casein protein act on LON in a similar fashion causing the morphology change of e.coli? Perhaps gluten causes an even stronger activation of LON?

I am trying to either go back to immunology school or find a lab willing to test this out for me.  This could explain the early stage of autoimmune disease where the antibodies are building up.  The infection changing morphologies is confusing the immune system. In some people the immune system is grabbing the gluten trigger because the infection keeps disappearing.

Once a person has developed a hyper antibody state a virus could easily push the immune system into a misguided attack.

What is elegant about this theory is that it could be also applied to autism.  The gluten casein pattern of sensitivity has been discussed for them and the sutterella bacteria that has been a suggested culprit is dimorphic.   Does the LON enzyme control it's morphology? Do the only kids who react to the viral vaccines already have the antibodies built up from sutterella switching morphologies? Is autism really an autoimmune disease of the brain?

This is where i am at now.  This is what we have to figure out.  I am optimistic. We just need to look at gluten and e.coli next.

I hope someone out there reads these and can understand me. Even better can someone out there test this out and give me an answer?

Angela Biggs