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 "Leaky Gut" as possible contributor to LBD? 
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post Re: "Leaky Gut" as possible contributor to LBD?
Here's the abstract for those who don't want to go to PubMed:

PLoS One. 2011;6(12):e28032. Epub 2011 Dec 1.
Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson's Disease.

Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, Estes JD, Dodiya HB, Keshavarzian A.
Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, Chicago, Illinois, United States of America.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder of aging. The pathological hallmark of PD is neuronal inclusions termed Lewy bodies whose main component is alpha-synuclein protein. The finding of these Lewy bodies in the intestinal enteric nerves led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. One potential mechanism for environmental toxin(s) and proinflammatory luminal products to gain access to mucosal neuronal tissue and promote oxidative stress is compromised intestinal barrier integrity. However, the role of intestinal permeability in PD has never been tested. We hypothesized that PD subjects might exhibit increased intestinal permeability to proinflammatory bacterial products in the intestine. To test our hypothesis we evaluated intestinal permeability in subjects newly diagnosed with PD and compared their values to healthy subjects. In addition, we obtained intestinal biopsies from both groups and used immunohistochemistry to assess bacterial translocation, nitrotyrosine (oxidative stress), and alpha-synuclein. We also evaluated serum markers of endotoxin exposure including LPS binding protein (LBP). Our data show that our PD subjects exhibit significantly greater intestinal permeability (gut leakiness) than controls. In addition, this intestinal hyperpermeability significantly correlated with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine, and alpha-synuclein as well as serum LBP levels in PD subjects. These data represent not only the first demonstration of abnormal intestinal permeability in PD subjects but also the first correlation of increased intestinal permeability in PD with intestinal alpha-synuclein (the hallmark of PD), as well as staining for gram negative bacteria and tissue oxidative stress. Our study may thus shed new light on PD pathogenesis as well as provide a new method for earlier diagnosis of PD and suggests potential therapeutic targets in PD subjects.


Mon Dec 12, 2011 11:17 pm
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Post Re: "Leaky Gut" as possible contributor to LBD?
Years ago when we learned that there were Lewy bodies in the enteric systems of those with PD, there was quite a bit of discussion about how this might be useful in diagnosing PD. There were at least two stumbling blocks -- how to safely biopsy patients to find evidence of alpha-synuclein protein in their guts, and how to get insurance companies to pay for this.

In this abstract, the authors state: "Our study may ... provide a new method for earlier diagnosis of PD and suggests potential therapeutic targets in PD subjects." I glanced through the paper but never found what new method they are suggesting. Is it the gut biopsy? Is it the sugar test for gut leakiness?

I found what the paper had to say about toxins to be very interesting. Is the theory now that PD is caused by toxins introduced into the gut? Previously one theory was that PD was caused by toxins introduced into the sinuses and brain through the nose.


Mon Dec 12, 2011 11:34 pm
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Post Re: "Leaky Gut" as possible contributor to LBD?
I have read that by the age of 80, 50% of us will have dementia. So if we are lucky(?) enough to live that long, we have a 50/50 chance of having some form of dementia. The odds go up the longer we live.

Without regard to family history, it makes sense for all of us to behave as if we might develop dementia. And also to hope for breakthroughs on the research front! Worrying about it is just stressful without any payoff.

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Jeanne, 68 cared for husband Coy, 86. RBD for 30+ years; LDB since 2003, Coy at home, in early stage, until death in 2012


Tue Dec 13, 2011 1:32 am
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Post Re: "Leaky Gut" as possible contributor to LBD?
Jeanne, I find that statistic extremely troubling. Looking back on my family, where most of my parents, grandparents and great-grandparents lived to be 80 or more and NONE had dementia, it has me concerned that there is some modern reason for this epidemic. Could it be medications? Environmental toxins? I'm not convinced it's just that 'we're living longer'.

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Pat [68] married to Derek [84] for 38 years; husband dx PDD/LBD 2005, probably began 2002 or earlier; late stage and in a SNF as of January 2011. Hospitalized 11/2/2013 and discharged to home Hospice. Passed away at home on 11/9/2013.


Tue Dec 13, 2011 1:56 am
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Post Re: "Leaky Gut" as possible contributor to LBD?
Pat, there may be environmental factors, but I do think that many more people living much longer is enough to account for it. We do not have statistics for earlier generations. Some people got "senile" but we don't even have statistics for that.

My grandmother was bedridden in a nursing home for her last few years. Looking back on what she was like I'm sure she had dementia in her 90s. Nobody said that. Nobody even said she was senile. She was just old and sick. She would not appear in any statistics if they had them then, and I'll bet very few family members would say, "Well, my grandmother had dementia." I wonder how often we don't think of the older generations of our families having dementia simply out of ignorance.

My other grandmother lived into her 90s also, and as far as I know (though I didn't see her often at the end) she did not have dementia. But out of my two grandmothers, 50% developed dementia. (Neither grandfather lived to 80.)

I never met my great-grandparents and I don't know what they died of, how long they lived, and whether they were of sound mind to the end.

Our grandchildren know Coy has dementia because they have been told. Otherwise based on their short visits will him they might not realize anything was wrong.

It is pretty hard to generalize about an entire generation from the few people we knew well enough to know whether they might have had dementia.

Pat, I was looking online at some statistics about what percentage of the population lived to 80, 90, and 100, in each decade since 1900. It was absolutely astounding how those percentages have grown. Yes, there have always been people who lived to 90. But, holy cow, they were more or less rare exceptions. Not any more!

If dementia is (with exceptions) a disease of old age, then more people reaching old age is going to greatly increase the incidence of dementia, even without any other contributing factors.

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Jeanne, 68 cared for husband Coy, 86. RBD for 30+ years; LDB since 2003, Coy at home, in early stage, until death in 2012


Tue Dec 13, 2011 2:27 am
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Post Re: "Leaky Gut" as possible contributor to LBD?
I think about this quite often now that I have almost completed my 80s. My next birthday in September will be my 90th. I test myself daily with the crossword puzzle in our daily newspaper. I believe I understand the news out of Washington, DC, [Maybe a little too well]. And so it goes.

DrP


Tue Dec 13, 2011 7:17 am
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Post Re: "Leaky Gut" as possible contributor to LBD?
My husband [and most of his family] have always had GI problems... And they also worship doctors and believe silver bullet pills exist for any and all ailments. When he was in his teens, a doctor started giving him Phenergen for his allergies. He took it for years. We were told when he was hospitalized for major depression and GAD 20 years ago that Phenergen is a tranquilizer. So all of this taken along with welding fumes, solvents and possible exposure to pesticides may be contributing factors. His mom (probable LBD) recently passed 20 days short of her 90th birthday. Two of his mom's sisters had some sort of dementia and the 3rd sister died young from cancer. Their father "regressed to infancy" in his late 60s. This is the grandfather that grandma said, "was the laziest man she ever knew." The "loss of initiative" coupled with "daytime sleepiness" would certainly look like a lazy person to someone who didn't know there was a disease process going on. On his paternal grandfather's side, there was what sounded like REM sleep disorder which my husband definitely has. I am thinking that the underlying genetics for LBD are possibly triggered by the environment - sooner as in my husband's case and later in his mom's case??? I wonder and wonder and wonder...
Baffled & Broken,
Roxanne

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My husband's first diagnosis in 2006 at age 64: Early Cortical Lewy Body Disease...


Tue Dec 13, 2011 4:12 pm
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Post Re: "Leaky Gut" as possible contributor to LBD?
The things I am reading suggest that most researchers think there is a genetic factor but that it is likely triggered by something in the environment. I applaud those who share this information with the younger generations. I think for my grandparent's generation, pride was such an important issue. As a result, most of us don't know the history of our families when it comes to dementia and, even more importantly, most of us have not been taught how to manage the care of our family elders. So much information is taught from one generation to the next. We learn much about parenting our children from previous generations, but so little information is passed on about how to help one's parents in cases of ill health and/or dementia. I applaud the transparency that exists on this list. I have been clueless about what to do, think, expect during my last year and a half since my mother showed up for my sister and myself to take care of. I hope that my kids learn from what we do so that if they are faced with this awful situation, they will not feel so lost.

Liz


Tue Dec 13, 2011 5:12 pm
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Post Re: "Leaky Gut" as possible contributor to LBD?
Quote:
Pat, there may be environmental factors, but I do think that many more people living much longer is enough to account for it. We do not have statistics for earlier generations. Some people got "senile" but we don't even have statistics for that.


It's not that the natural life span is increasing but that we are treating people for things that would have killed them off at a younger age before. [Also, fewer women die in childbirth and infant mortality has decreased]. Those who made it to 80 or 90 [e.g., John Adams, 90, and Thomas Jefferson, 83] were probably free from the afflictions we are routinely treated for today. So, let's say that my husband who was treated for many years for hypertension may have, untreated, died from a stroke in his 60's and never have developed dementia. In that sense, people are developing dementia because they are living longer than they would have without medical intervention.

_________________
Pat [68] married to Derek [84] for 38 years; husband dx PDD/LBD 2005, probably began 2002 or earlier; late stage and in a SNF as of January 2011. Hospitalized 11/2/2013 and discharged to home Hospice. Passed away at home on 11/9/2013.


Tue Dec 13, 2011 5:39 pm
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Post Re: "Leaky Gut" as possible contributor to LBD?
I'd love to have the medical histories of my ancestors. My dad & his mother developed obvious dementia symptoms at 86 - 87, my paternal great grandparents both lived to 89 and did not have dementia, and their ancestors whose graves I've been able to locate back to about 1800, died in their late 80's. But, there is no way of knowing if these people had dementia. It would be so fascinating (and helpful) if I had some data about their medical histories.
My mom and people in her family all died much younger from other things, so no way of knowing anything there. At least my kids will have a better idea of family medical histories, and hopefully that will help them some day.
Lynn

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Lynn, daughter of 89 year old dad dx with possiblity of LBD, CBD, PSP, FTD, ALS, Vascular Dementia, AD, etc., died Nov. 30, 2010 after living in ALF for 18 months.


Tue Dec 13, 2011 5:57 pm
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Post Re: "Leaky Gut" as possible contributor to LBD?
The best family medical histories are to be found in brain autopsy reports and body autopsy reports. Those are confirmed diagnoses.

I had no clue my dad had heart disease until we did a body autopsy. Info worth having!


Tue Dec 13, 2011 10:35 pm
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Post Re: "Leaky Gut" as possible contributor to LBD?
This is a very interesting discussion. My father also had the two factors people are mentioning here:

1. Digestive problems of all sorts, and
2. Took lots of pills from his doctors for all sorts of things my sister and I felt were unnecessary.


Wed Dec 14, 2011 1:31 pm
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Post Re: "Leaky Gut" as possible contributor to LBD?
It almost sounds like Lewy Bodies are formed by one's body in response to toxins???

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My husband's first diagnosis in 2006 at age 64: Early Cortical Lewy Body Disease...


Wed Dec 14, 2011 7:37 pm
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Post Re: "Leaky Gut" as possible contributor to LBD?
Roxanne,
We don't know if Lewy bodies are by-products of the neurodegeneration or causing the neurodegeneration. Also, in some people, there are genetic reasons why alpha-synuclein accumulates; in these cases, it seems that toxins don't play a role. Lots we don't know!
Robin


Wed Dec 14, 2011 8:06 pm
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Post Re: "Leaky Gut" as possible contributor to LBD?
robin wrote:
Lots we don't know!
Robin


Says the master of understatement ... :lol:

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Jeanne, 68 cared for husband Coy, 86. RBD for 30+ years; LDB since 2003, Coy at home, in early stage, until death in 2012


Wed Dec 14, 2011 9:10 pm
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