Inhalational Alzheimer's?

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
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Julie G
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Inhalational Alzheimer's?

Postby Julie G » Fri Feb 12, 2016 10:07 am

Inhalational Alzheimer's disease: An unrecognized - and treatable - epidemic
http://www.impactaging.com/papers/v8/n2 ... 00896.html

Here’s a new paper from Dr. Bredesen based on his clinical work. He’s found that mycotoxins (mold) may be the first direct cause of Alzheimer’s as opposed to a risk factor. Apparently, some of us may be more predisposed to this sub-type via our genetics- HLA-DR/DQ also associated with RA, EDS, T1D, Hashimoto's, etc. E4 carriers, because of our inherent pro-inflammatory response to pathogens, seem to have some protection.

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Stavia
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Re: Inhalational Alzheimer's?

Postby Stavia » Fri Feb 12, 2016 10:38 am

How very very interesting. Dr B certainly thinks outside the square.
Anyone know how to work out HLA typing from snps? I tried a year ago to see if I was gluten sensitive and hit a huge brick wall fast. Just couldn't do it and then couldn't be bothered.

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Re: Inhalational Alzheimer's?

Postby Gilgamesh » Fri Feb 12, 2016 12:59 pm

More brilliant hypothesizing!

Reminds me of how my CFIDS started, or might have started, years ago. (I'd been living in a room in a not-so-dry basement, and working in a room with an extremely old air-conditioning unit.)

Shoemaker has actually published quite a bit! I'd never heard of him.

G

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Re: Inhalational Alzheimer's?

Postby SusanJ » Sat Feb 13, 2016 9:33 am

Here's a quick summary of one variant associated with RA.

The HLA-DRB1 gene provides instructions for making a protein that plays a critical role in the immune system. The HLA-DRB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.


The HLA complex is the human version of the major histocompatibility complex (MHC), a gene family that occurs in many species. The HLA-DRB1 gene belongs to a group of MHC genes called MHC class II. MHC class II genes provide instructions for making proteins that are present on the surface of certain immune system cells. These proteins attach to protein fragments (peptides) outside the cell. MHC class II proteins display these peptides to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it triggers a response to attack the invading viruses or bacteria.

The protein produced from the HLA-DRB1 gene, called the beta chain, attaches (binds) to another protein called the alpha chain, which is produced from the HLA-DRA gene. Together, they form a functional protein complex called the HLA-DR antigen-binding heterodimer. This complex displays foreign peptides to the immune system to trigger the body's immune response.

Each MHC class II gene has many possible variations, allowing the immune system to react to a wide range of foreign invaders. Researchers have identified hundreds of different versions (alleles) of the HLA-DRB1 gene, each of which is given a particular number (such as HLA-DRB1*04:01).

Several common variations of the HLA-DRB1 gene are associated with a person's risk of developing rheumatoid arthritis. This disease causes chronic abnormal inflammation that primarily affects the joints. HLA-DRB1 is one of several genes in the HLA complex that have been associated with rheumatoid arthritis; variations of this gene are the most significant known genetic risk factor for the disease.

The HLA-DRB1 gene variations associated with an increased risk of rheumatoid arthritis affect single protein building blocks (amino acids) in the beta chain. These changes occur near the antigen-recognizing binding groove, which is the part of the protein that attaches (binds) to viral or bacterial peptides. This binding triggers the immune response that attacks foreign invaders. Although the mechanism by which HLA-DRB1 gene variations increase the risk of rheumatoid arthritis is unclear, researchers suspect it is related to changes in peptide binding that stimulate an abnormal immune response. However, many other genetic and environmental factors also contribute to a person's overall risk of developing rheumatoid arthritis.

http://ghr.nlm.nih.gov/gene/HLA-DRB1

The alleles of the HLA-DRB1*0401 variation are rs660895 (G/C is risk), rs6910071 (G/C is risk) and rs3817964 (A/T is risk).

But as they note above, there are "hundreds of different versions (alleles) of the HLA-DRB1 gene". I'll dig around in my notes and see if I can find alleles for celiac, since I looked at that extensively a few years back.
Last edited by SusanJ on Sat Feb 13, 2016 6:46 pm, edited 1 time in total.
Reason: Clarify risk alleles.

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Re: Inhalational Alzheimer's?

Postby Thx4thegenes » Sat Feb 13, 2016 5:19 pm

Thank you Susan for your work. After researching about the Vitiligo that I have, I asked my doctor to test me for HLA-B27, which was positive. I'm guessing this is all connected somehow, the HLA region. She did mention that I am susceptible to inflammation due to heredity. There wasn't much info on 23 and me regarding HLA DR/DQ. I checked the snp's you mentioned and I am AG, AA and TT respectively. "Wild" meaning, not so good? My grandmother had RA. All in the family! : )

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Re: Inhalational Alzheimer's?

Postby SusanJ » Sat Feb 13, 2016 6:45 pm

For rs660895 and rs6910071, G (or C) is the risk allele. Wild type (A) is the allele most likely to be found in the general population. Usually the variant (or mutant) allele is associated with disease.

For rs3817964 T is the risk allele.

I've edited my original post, to be more clear.

http://snpedia.com/index.php/Rs660895
http://snpedia.com/index.php/Rs6910071
http://snpedia.com/index.php/Rs3817964
Last edited by SusanJ on Tue Mar 01, 2016 8:05 am, edited 1 time in total.
Reason: Updated risk allele

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Re: Inhalational Alzheimer's?

Postby circular » Sat Feb 13, 2016 9:24 pm

Don't have time to look it up, but I'm quite sure there's recent research indicated some HLA genes come from Neanderthals if anyone wants to google it for fun :-)
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: Inhalational Alzheimer's?

Postby ApropoE4 » Sat Feb 13, 2016 11:42 pm

I can see how this would be missed by one researcher, but I wonder how the co-authors didn't point out that there is no record of elevated incidence of AD like dementia in environments that are rich in aspergillus and such other than through acute toxicity.

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Re: Inhalational Alzheimer's?

Postby Julie G » Sat Feb 27, 2016 7:09 pm

ApropoE4, great point. I also wondered about this from an epidemiological perspective. From what I’ve learned, the geographic specific presentation wouldn’t necessarily appear as not everyone is susceptible. This appears to be a case of specific genetic predisposition (about 1/4 of HLA-DQ/DR haplotypes) intersecting with exposure to mycotoxins that results in what Dr. Bredesen is calling Inhalational AD.
Since the majority of patients with CIRS have a combination of genetic sensitivity plus exposure to a complex aerosolic mixture of mycotoxins, spores, bacteria, microbial fragments, inflammagens, volatile organic compounds, and other molecular species, the majority of patients with type 3 Alzheimer’s disease and CIRS are likely to have an inhalational cause of Alzheimer’s disease (IAD).

Those who carry the HLA-DQ/DR haplotype and also exhibit a specific constellation of chronic inflammatory response syndrome/CIRS symptoms and laboratory abnormalities are suspect. The paper also points out that there are other known causes of CIRS such as biotoxins, from the Borrelia burgdorferi of Lyme disease or from other tick-borne pathogens, or aquatoxins such as those from dinoflagellates. Wild speculation on my part, but I wonder if there are OTHER as yet unidentified causes (lectins, other dietary sensitivities, viruses, etc.) that can also result in a CIRS presentation in those who are genetically predisposed.

Dr. Bredesen was very interested to learn that many of us exhibit mast cell activation/MCA symptoms that overlap with CIRS symptoms. Because I have BOTH a history of MCA and an innate immune dysfunction (hypogammaglobulinemia,) he’s recommending that I have the following labs run to see if I fall into the susceptible category:

HLA-DR/DQ: LabCorp code 167120
TGF-beta-1: Quest code 52112
MSH: LabCorp code 010421
NJC-C4a: Quest code 42658

Dr. Bredesen suggests that anyone with MCA or CIRS symptoms have the above tests run. Apparently those who carry this genetic susceptibility are predisposed to not only Type 3, but ALL all of the subtypes he’s identified :shock:. I find it fascinating that Ehler-Danlos Syndrome/EDS folks (like me) have been found to carry a version of the HLA-DQ/DR haplotype. I’m struggling to wrap my head around Dr. Bredesen's description of this evolving clinical presentation that he’s repeatedly encountering. I agree with his analysis that at some point things are more than chance or coincidence.

Coincidentally, Chris Kresser recently shared that his family was exhibiting symptoms of mycotoxin exposure. He just did a podcast on getting your house tested for mold and other mycotoxins. Here’s a link to both the podcast & transcript:
http://chriskresser.com/how-to-test-you ... f45c32283b

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Re: Inhalational Alzheimer's?

Postby deno » Sun Feb 28, 2016 8:23 am

I have seen several articles associating fungus in the brain with Alzheimer's such as http://www.nature.com/articles/srep15015. Since mold is a fungus could there be some connection?
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