Endotoxin (LPS) May Be A Causative Factor In Alzheimer Disease (AD)

haidut

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I posted recently about a study that found many of the chronic degenerative diseases can be traced back to endotoxin and excess iron.
Endotoxin And Iron Finally Recognized As Potential Causes Of Many Diseases

This study went a step further and identified endotoxin (LPS) in the brains of AD patients. While the authors say further research is needed to confirm that LPS is in fact causative for AD, there is enough evidence from animal studies to support that connection. If endotoxin is indeed causative, then inhibiting its release through carrot salad and charcoal, or blocking its effects with TLR4 antagonists may be preventative and therapeutic for AD.

Gram-negative bacterial molecules associate with Alzheimer disease pathology
http://www.newswise.com/articles/gram-negative-bacteria-may-influence-alzheimer-s-disease-pathology
"...Many Gram-negative bacteria are pathogenic, including E. coli, Helicobacter pylori, salmonella, Chlamydophila pneumoniae and Shigella. Researchers have known for some time that infections can increase the risk of Alzheimer’s; however, this is the first time anyone has found increased levels of Gram-negative bacteria antigens in Alzheimer’s disease brains and bacterial molecules associated with the disease pathology. This research follows previous animal studies in the Sharp lab that showed bacterial LPS plus ischemia/hypoxia can increase amyloid β and produce amyloid plaque-like aggregates."

"...The study compared 24 gray and white matter samples from patients with the disease – using Consortium to Establish a Registry for Alzheimer’s disease criteria – with 18 samples from people who had shown no evidence of cognitive decline. While LPS and K99 were found in both groups, the prevalence was much higher in the Alzheimer’s patients. K99 was found in nine of 13 Alzheimer’s gray-matter samples compared to one of 10 controls by Western blot analysis. Increased K99 levels were also found in Alzheimer’s disease white matter samples. The story was similar with LPS, which was found in all six samples (three gray and three white matter) but not in the controls by Western blot analysis."

"...These findings highlight the need to further investigate how infectious agents impact Alzheimer’s. While discovering LPS and K99 in Alzheimer’s disease brain samples is a good start, researchers must study the role bacteria may play in the disease pathology. A proven link between bacterial infections and Alzheimer’s could offer new opportunities to prevent and treat the disease. “If LPS is causative, we could immunize against LPS or treat Gram-negative infections more vigorously than we normally do,” Sharp said."
 

Makrosky

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Nice post haidut, thanks!

How is it possible that LPS can cross the blood-brain barrier ?
 

haidut

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Nice post haidut, thanks!

How is it possible that LPS can cross the blood-brain barrier ?

Well, hypothyroidism and aging increases vascular permeability and reduces the function of the BBB. So, for older people the risk of LPS to the brain may be much bigger, but I think even in younger people it is visible quite readily. People running to exhaustion have unmistakable neurological symptoms for a few hours after the run, and they are quite similar to LPS overload in the brain.
Btw, LPS itself increases BBB permeability thus making it easier for itself (and other toxic mediators) to get through.
Lipopolysaccharide-induced blood brain barrier permeability is enhanced by alpha-synuclein expression. - PubMed - NCBI
Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit
Effect of LPS on the permeability of the blood–brain barrier to insulin
 

Makrosky

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Well, hypothyroidism and aging increases vascular permeability and reduces the function of the BBB. So, for older people the risk of LPS to the brain may be much bigger, but I think even in younger people it is visible quite readily. People running to exhaustion have unmistakable neurological symptoms for a few hours after the run, and they are quite similar to LPS overload in the brain.
Btw, LPS itself increases BBB permeability thus making it easier for itself (and other toxic mediators) to get through.
Lipopolysaccharide-induced blood brain barrier permeability is enhanced by alpha-synuclein expression. - PubMed - NCBI
Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit
Effect of LPS on the permeability of the blood–brain barrier to insulin

****... really... I couldn't imagine such a big molecule could cross the BBB. Good links professor haidut.

Now if this crosses the BBB no matter how much you block the TLR4 receptor it is not gonna be good, really. I know you posted a study about rats withour a TLR4 receptor (genetically mutated) being immune to endotoxin but such a big molecule inside the brain is NO BUENO for sure, isn't it ?
 

haidut

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****... really... I couldn't imagine such a big molecule could cross the BBB. Good links professor haidut.

Now if this crosses the BBB no matter how much you block the TLR4 receptor it is not gonna be good, really. I know you posted a study about rats withour a TLR4 receptor (genetically mutated) being immune to endotoxin but such a big molecule inside the brain is NO BUENO for sure, isn't it ?

It is certainly no bueno to have LPS in the brain. It means the BBB is severely disrupted and even bacteria can possible get through and form a (potentially lethal) infection. But blocking TLR4 in the brain should still be beneficial as another study I posted on opioids shows. Morphine and other opioids actually make a person more sensitive to pain in the long run as they act as TLR4 agonists in the brain and cause chronic inflammation. So, if AD is primarily an inflammatory disorder, blocking TLR4 should be therapeutic even though the issue of disrupted BBB may not be solved.
 

milk_lover

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I understand the importance of opposing endotoxins but I can't stand the taste of any of antiseptic vegetables like carrots and bamboo shoot. And charcoal causes constipation for my case even at low doses. The aged cascara is hard to obtain.

I am instead fighting the endotoxin by vitamin D, cypro, aspirin, glycine, taurine, pregnenolone, coffee etc.,. Would those suffice? Or do i need to get back to my undelicious carrot salad?
 

milk_lover

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@milk_lover Have you tried mushrooms? I couldn't face carrot after a week or two, but have no problems with mushrooms boiled in salted water.
I have but it takes a long time to prepare. I am at the office most of the day. Did you get any benefit from them? And how long do you boil them?
 

Dante

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I posted recently about a study that found many of the chronic degenerative diseases can be traced back to endotoxin and excess iron.
Endotoxin And Iron Finally Recognized As Potential Causes Of Many Diseases

This study went a step further and identified endotoxin (LPS) in the brains of AD patients. While the authors say further research is needed to confirm that LPS is in fact causative for AD, there is enough evidence from animal studies to support that connection. If endotoxin is indeed causative, then inhibiting its release through carrot salad and charcoal, or blocking its effects with TLR4 antagonists may be preventative and therapeutic for AD.

Gram-negative bacterial molecules associate with Alzheimer disease pathology
http://www.newswise.com/articles/gram-negative-bacteria-may-influence-alzheimer-s-disease-pathology
"...Many Gram-negative bacteria are pathogenic, including E. coli, Helicobacter pylori, salmonella, Chlamydophila pneumoniae and Shigella. Researchers have known for some time that infections can increase the risk of Alzheimer’s; however, this is the first time anyone has found increased levels of Gram-negative bacteria antigens in Alzheimer’s disease brains and bacterial molecules associated with the disease pathology. This research follows previous animal studies in the Sharp lab that showed bacterial LPS plus ischemia/hypoxia can increase amyloid β and produce amyloid plaque-like aggregates."

"...The study compared 24 gray and white matter samples from patients with the disease – using Consortium to Establish a Registry for Alzheimer’s disease criteria – with 18 samples from people who had shown no evidence of cognitive decline. While LPS and K99 were found in both groups, the prevalence was much higher in the Alzheimer’s patients. K99 was found in nine of 13 Alzheimer’s gray-matter samples compared to one of 10 controls by Western blot analysis. Increased K99 levels were also found in Alzheimer’s disease white matter samples. The story was similar with LPS, which was found in all six samples (three gray and three white matter) but not in the controls by Western blot analysis."

"...These findings highlight the need to further investigate how infectious agents impact Alzheimer’s. While discovering LPS and K99 in Alzheimer’s disease brain samples is a good start, researchers must study the role bacteria may play in the disease pathology. A proven link between bacterial infections and Alzheimer’s could offer new opportunities to prevent and treat the disease. “If LPS is causative, we could immunize against LPS or treat Gram-negative infections more vigorously than we normally do,” Sharp said."

When i read this news on the net, i knew i would find this post on the ray peat forum by haidut next morning
 

raypeatclips

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I have but it takes a long time to prepare. I am at the office most of the day. Did you get any benefit from them? And how long do you boil them?

I agree carrot salad is vastly more convenient to make. I noticed better/more frequent bowel movements when I eat them regularly. I boil a few packets together, usually about 600g, for an hour. Then store in fridge and eat 100-150g at a time heated up in the microwave.
 

haidut

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When i read this news on the net, i knew i would find this post on the ray peat forum by haidut next morning

How did you find this on the news outlets? As far as I can see it is not on the major ones, so just curious where you saw it on.
 

haidut

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Pet Peeve

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I am instead fighting the endotoxin by vitamin D, cypro, aspirin, glycine, taurine, pregnenolone, coffee etc.,. Would those suffice? Or do i need to get back to my undelicious carrot salad?

Protein helps the liver deal with endotoxins
 

Dante

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Yeah i posted the same link above, pretty sure there is going to be a thread on it and we might see an other discussion based on sterile vs non-sterile gut
 
Last edited:

stargazer1111

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I posted recently about a study that found many of the chronic degenerative diseases can be traced back to endotoxin and excess iron.
Endotoxin And Iron Finally Recognized As Potential Causes Of Many Diseases

This study went a step further and identified endotoxin (LPS) in the brains of AD patients. While the authors say further research is needed to confirm that LPS is in fact causative for AD, there is enough evidence from animal studies to support that connection. If endotoxin is indeed causative, then inhibiting its release through carrot salad and charcoal, or blocking its effects with TLR4 antagonists may be preventative and therapeutic for AD.

Gram-negative bacterial molecules associate with Alzheimer disease pathology
http://www.newswise.com/articles/gram-negative-bacteria-may-influence-alzheimer-s-disease-pathology
"...Many Gram-negative bacteria are pathogenic, including E. coli, Helicobacter pylori, salmonella, Chlamydophila pneumoniae and Shigella. Researchers have known for some time that infections can increase the risk of Alzheimer’s; however, this is the first time anyone has found increased levels of Gram-negative bacteria antigens in Alzheimer’s disease brains and bacterial molecules associated with the disease pathology. This research follows previous animal studies in the Sharp lab that showed bacterial LPS plus ischemia/hypoxia can increase amyloid β and produce amyloid plaque-like aggregates."

"...The study compared 24 gray and white matter samples from patients with the disease – using Consortium to Establish a Registry for Alzheimer’s disease criteria – with 18 samples from people who had shown no evidence of cognitive decline. While LPS and K99 were found in both groups, the prevalence was much higher in the Alzheimer’s patients. K99 was found in nine of 13 Alzheimer’s gray-matter samples compared to one of 10 controls by Western blot analysis. Increased K99 levels were also found in Alzheimer’s disease white matter samples. The story was similar with LPS, which was found in all six samples (three gray and three white matter) but not in the controls by Western blot analysis."

"...These findings highlight the need to further investigate how infectious agents impact Alzheimer’s. While discovering LPS and K99 in Alzheimer’s disease brain samples is a good start, researchers must study the role bacteria may play in the disease pathology. A proven link between bacterial infections and Alzheimer’s could offer new opportunities to prevent and treat the disease. “If LPS is causative, we could immunize against LPS or treat Gram-negative infections more vigorously than we normally do,” Sharp said."

This makes sense to me. Ever since my ketogenic diet days, when I eat things that cause symptoms of endotoxemia, I get short-term memory problems and a lot of times my train of thought will just stop and I'll forget what I was doing or saying.

This goes away if I avoid endotoxin-producing or releasing foods. It scared the crap out of me when it started happening. I was happy when I figured out that avoiding certain foods and drinking lots of milk (I think the oligosaccharides in it feed the beneficial bacteria) make it go away.
 
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