Nigerian Alzheimer's Paradox?

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
JNB
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Re: Nigerian Alzheimer's Paradox?

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AnnieV wrote: Mon Apr 29, 2024 6:40 pm
I have read about the parasite theories but what exactly, in specific language do parasites do that supposedly help?
I'm convinced that helminths hack body to produce T regulatory cells (Treg cells) so that host immune system won't attack them and also won't attack its own tissues where parasite is attached to.
Please ref to my posts here:
viewtopic.php?p=91520#p91520
and here
viewtopic.php?p=91421#p91421
I especially love this one
Baby rats with tapeworms avoided the brain inflammation that plagued worm-free rats after exposure to immune triggers in adulthood. What’s more, the benefits began early, while still in the womb. Expectant mother rats with tapeworms passed similar protection on to their worm-free pups, the researchers found.
They also didn’t develop the same memory problems later in life that their worm-free counterparts did.


I believe that T- cells are the key to nerodegeneration.


And probably not only that, I believe parasites may also release some enzymes that can help them break down certain host proteins that are essential for their metabolism. This might have an effect on breaking amyloid beta protein (clearing up the plaque) and also possibly on tau protein as well.
Note, no evidence here, just pure my gut feeling.

I'm convinced that APOE4 has the strongest innate immune reactions, that can be fueled by increased LDL cholesterol.
In experiments with mice possessing one of each of the versions of the gene, he and colleagues found tumors in those with ApoE4 grew the smallest and spread the least.

ApoE4 is the most effective version of ApoE in terms of enhancing the immune response to tumor cells. Compared to animals with other variants, the mice carrying ApoE4 showed a greater abundance of tumor-fighting T cells recruited into the melanoma tumor, as well as reduced blood vessels.

Genetic data from more than 300 human melanoma patients echoed the mouse experiments: On average, people with ApoE4 survived the longest, while those with ApoE2 lived the shortest.
Study reveals first evidence inherited genetics can drive cancer’s spread

My theory is that if APOE4 immune system is not tamed/cushioned well it can easily turn guns against itself...
So maybe it's not that much about diet than environment we live in....
Last edited by JNB on Tue Apr 30, 2024 4:40 am, edited 5 times in total.
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Re: Nigerian Alzheimer's Paradox?

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I have read about the parasite theories but what exactly, in specific language do parasites do that supposedly help?
From what I understand, E4 carriers have overly activated innate immune systems. Parasites "dampen" that effect (reducing inflammation/improving cognition) by giving our immune systems a job. This is a great example of E4 carriers thriving in a genetically compatible environment. Read more here: Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden
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Re: Nigerian Alzheimer's Paradox?

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JNB wrote: Tue Apr 30, 2024 2:59 am So maybe it's not that much about diet than environment we live in....
Isn't diet changing more than parasitic load as rates of neurological disease accelerate in [relatively] recent years? I'm just starting the Price book (wow!) so am curious to see what his research revealed about that.
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Re: Nigerian Alzheimer's Paradox?

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OfficeSpace wrote: Tue Apr 30, 2024 7:07 am
Isn't diet changing more than parasitic load as rates of neurological disease accelerate in [relatively] recent years? I'm just starting the Price book (wow!) so am curious to see what his research revealed about that.
Of course there are many factors beyond APOE4 that contribute to neurodegeneration like diet extensive sugar, and saturated fat intake (empty calories), pesticides, chemical toxins, plastics, heavy metals, highly processed foods, air pollution, excessive drinking, smoking, chronic stress (existential stress), social media, society, loneliness, physical inactivity, sleep deprivation. It all maters.
You can manage some of these but you can hardly escape all of these factors.
Now why I love this Tsimane article because these people have organic food all around, they have low stress, lots of physical activity, low fat and sugar intake (mostly complex carbohydrates with high quality meats), low blood pressure, no diabetes, low lipid levels and yet you can still see improved cognition in APOE4 with mild or high helminths activity (with higher worms activity APOE4 outperforms APOE3 without worms!) and APOE4 has worsened cognition with no parasitic activity within the same diet and environment.
So my guess is that worms are critical for brain health in general for APOE4 (or rather their effect on our immune system). And it may be more important than diet itself.
It's gross I know (even for me) and nobody can listen to this in my family and nor even close friends. My mother she has horrible join pain but she cannot stand listening anything about worms.
We would like to see science that can provide us pills that mimic worms activity and then we can happily pay for that. That's what we love.
But this may take decades.
Last edited by JNB on Wed May 01, 2024 4:48 am, edited 1 time in total.
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Re: Nigerian Alzheimer's Paradox?

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Julie G,

Thanks much for the article! Can we dive deeper into the specific “parasite” “benefit” question?

The abstract’s quote, “Contrary to observations in industrial populations, older adult E4 carriers with high parasite burdens either maintained or showed slight improvements in cognitive performance, whereas non-E4 carriers with a high parasite burden showed reduced cognitive performance. Being an E4 carrier is the strongest risk factor to date of AD and cognitive decline in industrial populations; it is associated with greater cognitive performance in individuals facing a high parasite and pathogen load, suggesting advantages to the E4 allele under certain environmental conditions.” That's fascinating, good news, and fully consistent with Nature’s/God’s original design and evolution, there’s at least this benefit why APOE4 was the original and enduring design. That observation now begs further analysis: What specific parasite species are supposedly “beneficial” among APOE4 carriers (compared to non-carriers)? Thankfully the study answers that question by stating, “Instead of focusing on single species of parasite, eosinophils are used as a biomarker of parasitic infection more generally”--The study used biomarkers of parasitic burden to presence, specifically via eosinophil counts, “A manual leukocyte count and 5-part differential were collected immediately after a blood-collection, and erythrocyte sedimentation rate (ESR) was assessed by using the Westergren method (39). Eosinophil counts measured via manual 5-part differential were used as an index of parasitic infections, as they relate to both current and past history of multiple types of parasitic infections (42, 43). Although hookworm, which induces T-helper 2 response characterized by eosinophilia (43), is the most common helminth seen in 56% of Tsimane (39, 40), eosinophilia is provoked by parasitic infections of many different types.” Great. So now we have to ask what exactly triggered the eosinophilia, how exactly did the parasites trigger that process? The study does not say. But if we assume parasites are “takers” and not “givers” (hence the name parasite) of anything is it then reasonable to presume that parasites’ waste products triggered the eosinophilia, which leads to the benefit for APOE4 carriers? So what exactly are those waste products that somehow could be the basis of the benefit from parasites for APOE4 carriers? (And does it not seem the “parasites” really aren't parasitic per se but more akin to a symbiotic relationship at least as evidenced by the demonstrated cognitive benefit for APOE4 carriers?)
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Re: Nigerian Alzheimer's Paradox?

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This seems to be a relatively simple set of experiments. Extract the molecules from parasites and identify the factors which reduce the immune response. Then put it in a pill, or more likely an injection. Someone, somewhere must have done this. I haven't had time to look, but I'll put it on my list. :)
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Re: Nigerian Alzheimer's Paradox?

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Fiver wrote: Wed May 01, 2024 10:47 am This seems to be a relatively simple set of experiments. Extract the molecules from parasites and identify the factors which reduce the immune response. Then put it in a pill, or more likely an injection. Someone, somewhere must have done this. I haven't had time to look, but I'll put it on my list. :)
I found one promising article
Maizels and his team found that parasitic worms increase numbers of a certain type of immune cell. It’s called a regulatory T-cell, or T-Reg for short. “They’re like the police officers of the immune system,” says Maizels. They keep things calm so that the body doesn’t react too strongly to foods, pollen and other harmless bits of the environment.

The really exciting thing about T-Regs, though, is that they lower inflammation. Inflamed tissue tends to get red and swollen. That’s because the body has sent extra blood to this area that is enriched with immune cells. These immune cells fight off infection. But they can damage healthy cells in the process. Sometimes, inflammation happens even where there is no infection to fight. This is one of the root causes of a huge number of diseases, including diabetes and heart disease.

Loukas and his team want to be able to treat inflammation without needing to infect anyone. So they’re trying to mimic whatever it is the worms do to increase T-Regs. The team collects the substances hookworms give off as they feed. “Many people call it worm spit or worm vomit,” he says. They find proteins in the stuff and study them. One protein they found increases the number of T-Regs in mice and in human cells they’ve studied in the lab. Someday, it could lead to new therapies for diseases that involve too much inflammation. Loukas founded a company, Macrobiome Therapeutics, which is working to develop such treatments.
Image
And worms aren’t the only creepy-crawly things that like to live inside the gut. The microbiome is a name for the community of all microscopic critters — mainly bacteria — that live inside us. Which bacteria colonize our gut can impact our health. In general, the more different types, the better. Worm infections tend to change which bacteria call the gut home. Some of these changes can be harmful. But in other cases, they might offer benefits. One 2016 study found that a worm infection could protect mice from an inflammatory bowel disease (Crohn’s disease). The worm infection made it harder for disease-causing bacteria to thrive.
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Re: Nigerian Alzheimer's Paradox?

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Keyword is BACTERIA! "Worm infections tend to change which bacteria call the gut home. Some of these changes can be harmful. But in other cases, they might offer benefits. One 2016 study found that a worm infection could protect mice from an inflammatory bowel disease (Crohn’s disease). The worm infection made it harder for disease-causing bacteria to thrive." So what other things, besides perhaps greater parasite populations, are native to the Nigerian (and other Sub-Saharan cultures) diets that contain healthful bacteria that western-industrialized cultures largely don't, no longer have?
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Re: Nigerian Alzheimer's Paradox?

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AnnieV wrote: Fri May 03, 2024 10:26 am Keyword is BACTERIA! "Worm infections tend to change which bacteria call the gut home. Some of these changes can be harmful. But in other cases, they might offer benefits. One 2016 study found that a worm infection could protect mice from an inflammatory bowel disease (Crohn’s disease). The worm infection made it harder for disease-causing bacteria to thrive." So what other things, besides perhaps greater parasite populations, are native to the Nigerian (and other Sub-Saharan cultures) diets that contain healthful bacteria that western-industrialized cultures largely don't, no longer have?
Here is one article that goes really deep into gut microbiome.

We identified 124 gut-resident species vanishing in industrialized populations and highlighted distinct aspects of the Hadza gut microbiome related to in situ replication rates, signatures of selection, and strain sharing. Industrialized gut microbes were found to be enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes.
Industrialized populations are characterized by low microbiome diversity. Aspects of lifestyle, including (1) consumption of highly processed foods, (2) high rates of antibiotic administration, (3) birth via cesarean section and use of baby formula, (4) sanitation of the living environment, and (5) reduced physical contact with animals and soil, have been hypothesized to mediate this reduced diversity.2 These aspects are absent from the lifestyle of non-industrialized human populations, including hunter-gatherers, who harbor extremely high microbiome diversity.3 The transition to an industrialized microbiome is also observed in immigrants to the United States of America, supporting a causal role of lifestyle in altering microbiome composition.4
Image

And I think many people are below an average Californian
gut microbiota diversity of AD patients was significantly decreased compared to that of controls
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Re: Nigerian Alzheimer's Paradox?

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Fiver wrote: Wed May 01, 2024 10:47 am This seems to be a relatively simple set of experiments. Extract the molecules from parasites and identify the factors which reduce the immune response. Then put it in a pill, or more likely an injection. Someone, somewhere must have done this. I haven't had time to look, but I'll put it on my list. :)
I've found one,
Here, based on target-driven discovery strategy, we successfully identified a small 3 kDa peptide (SjDX5-53) from egg extracts of schistosome, which promoted both human and murine Tregs production. SjDX5-53 presented immunosuppressive function by arresting dendritic cells (DCs) at an immature state and augmenting the proportion and suppressive capacity of Tregs. In mouse models, SjDX5-53 protected mice against autoimmune-related colitis and psoriasis through inducing Tregs and inhibiting inflammatory T-helper (Th) 1 and Th17 responses.
But really thinking whether regular "controlled" injecting is just less troublesome than having some real parasites inside that work all the time pretty much effortless.
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