NY Times article on theory that parasitic infection may be reason APOE4 was once protective

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BrianR
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Re: NY Times article on theory that parasitic infection may be reason APOE4 was once protective

Post by BrianR »

I read a Science Daily summary of a new paper about the Tsimane: Nutrition transition in two lowland Bolivian subsistence populations (Supplements) which I thought was interesting due to their High Carb diets and excellent cardiovascular status.

Quoting from the paper, emphasis is mine.

The Tsimane diet consisted primarily of 26 types of cultigens (61.9% of average daily calories/person), 43 species of fish (15.6%), 32 species of wild game (6.1%), meat from domesticated animals (7.5%), 15 varieties of wild fruit and vegetables (0.7%), and 17 types of market foods (8.1%) (Supplemental Table 5). Main horticultural staples included plantains (60.2% of cultigen calories), rice (18.8%), manioc root (14.0%), and corn (5.2%).
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Compared with Moseten and US populations, the Tsimane diet contained a high proportion of carbohydrates (63–65% of total caloric intake) and low amounts of fat (15%) (Figure 3). Daily intakes of saturated, monosaturated, and polyunsaturated fats were 39–44%, 46–53%, and 42–44%, respectively, of US amounts (Table 1). Protein intake was higher among Tsimane (20–21%) and Moseten (20–23%) than Americans (16%). Sex differences in proportional macronutrient intake were minor in all populations.
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The Tsimane estimated intake of magnesium, potassium, and selenium far exceeded US and Moseten amounts. Tsimane daily fiber intake was also 1.5–2 times higher than US or Moseten intakes. Yet, intakes of dietary sodium, calcium, and vitamins E, D, and K among Tsimane and Moseten were much lower than among Americans.

See Table 1 in the paper for more details on macro/micro nutrients. The researchers do seem to have guessed at some of the micronutrient levels, perhaps that explains some of the significant differences.

I speculate that significant amounts of exercise through the day may explain some of the positive outcomes. Perhaps ongoing parasite infections which modulate or redirect the immune system play a role.

Or perhaps we should make foods with resistant starches be a very significant percentage of our daily calories. (And keep the saturated fats quite low.)
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Re: NY Times article on theory that parasitic infection may be reason APOE4 was once protective

Post by mike »

Lucy5 wrote:Thus, a role for APOE4 in protecting aborigines from parasites most likely stems from the excess beta-amyloid it engenders in the brain, leading to more antimicrobial protection. The resulting increase in amyloid generation would then later increase risk for AD.
So this is saying that the existence of beta-amyloid provides protection when young!? Not just that it caught up some nasty, but it in itself is beneficial?
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Re: NY Times article on theory that parasitic infection may be reason APOE4 was once protective

Post by Lucy5 »

Mike wrote: So this is saying that the existence of beta-amyloid provides protection when young!? Not just that it caught up some nasty, but it in itself is beneficial?
Lucy wrote: Thus, a role for APOE4 in protecting aborigines from parasites most likely stems from the excess beta-amyloid it engenders in the brain, leading to more antimicrobial protection
Hey Mike - I had to refresh my memory on this one! It's a line from the 2017 response written by Drs Robert Moir & Rudy Tanzi (at the request of the CureAlz fund) to the subject NYT op-ed discussing the theory that the E4 allele may provide protection from certain parasitic infections via increased amyloid beta response. Among other clarifications, the good docs pointed out the downside of that protection was a higher risk of dementia later in life due to this increased amyloid burden. So, regardless of my two 4s, I'd still opt for avoiding parasites!
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Re: NY Times article on theory that parasitic infection may be reason APOE4 was once protective

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I read these studies with great interest. I understand the theory but I rarely come across strong data showing that E4 carriers have greater protection against parasites or other infections. It's not been my observation from limited personal experience.

My current non-expert way of thinking about this is that E4 shifts the overall physiology of cells in a way that could confer indirect protection to a limited degree.

It's entirely possible I'm uninformed and overly-skeptical. I definitely see how E4 impacts the immune system and related responses.....I totally get how amyloid is a part of the innate immune system...what I haven't seen are studies showing that infection rates are lower in E4s in nature or that they survive outbreaks better. This would be something at least, for E4s.

I'd like to learn more. Could anyone suggest a study or review article I could read on this? Something with a data-set comparing disease or infection rates in E2,E3,vs E4 carriers? Thanks!
Last edited by Fiver on Tue Nov 06, 2018 10:56 am, edited 1 time in total.
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Re: NY Times article on theory that parasitic infection may be reason APOE4 was once protective

Post by mike »

So it is just that there are more beta-amyloid in E4s, and that is what is protective. What I didn't get, it sounds like in non-infected E4 individuals lost mental ability, while infected E4s kept up their mental ability...!?
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Re: NY Times article on theory that parasitic infection may be reason APOE4 was once protective

Post by BrianR »

mike wrote:So this is saying that the existence of beta-amyloid provides protection when young!? Not just that it caught up some nasty, but it in itself is beneficial?
Mike, not quite what you're asking for, but this informative general review of APOE: APOE genotype and stress response - a mini review in the section "APOE genotype and the inflammatory response" asserts the following APOE4 immune related benefits:

"However, it should be noted that, though the heightened inflammatory response in presence of APOE ε4 may be deleterious to the organism with advanced age, it may confer greater protection from pathogens early in life (“antagonistic pleiotropy” theory, [124]). Indeed, a still quite high prevalence of APOE ε4 is still observed in certain indigenous populations, including Pygmies, Khoisan, and aborigines of Malaysia and Australia, where APOE ε4 frequency ranges from 24 to 40.7 % [125]. Interestingly, spontaneous abortions [126] and still-births [127] were found to be less frequent in APOE ε4 allele carriers, suggesting that APOE4 somehow protects the developing embryo [126, 127]. Furthermore, Oriá et al. [128] reported positive effects of APOE ε4 on the cognitive and physical development in children who suffered from heavy diarrhea in early childhood in a slum region in Brazil, where malnutrition is common [128, 129, 130]. Moreover, APOE ε4 appeared beneficial in certain infectious diseases evoked by both viruses (e.g., hepatitis C, HCV) and bacteria (e.g., malaria) [131, 132, 133], though, on the contrary seemed rather detrimental in the case of human immunodeficiency virus (HIV) and herpes simplex virus (HSV) infections [134, 135] (reviewed in [136])."

So, with regard to Aβ, which I understand to be part of the innate immune system, it's kind of like when the zombies break into your house and the weapon you have at hand is a flame thrower. It solves the short term crisis and keeps you alive, but, repeated use in the long run may not be so great for your house.
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Re: NY Times article on theory that parasitic infection may be reason APOE4 was once protective

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mike wrote:So it is just that there are more beta-amyloid in E4s, and that is what is protective. What I didn't get, it sounds like in non-infected E4 individuals lost mental ability, while infected E4s kept up their mental ability...!?
Mike, are you referring to this?
"Sure enough, he found that Tsimane with infections were more likely to maintain their mental fitness if they carried one or two copies of the ApoE4 gene; for them, the “Alzheimer’s gene” provided an advantage. For the minority who’d managed to elude parasitic infection, however, the opposite was true, and the ApoE4 gene was connected with cognitive decline, just as it is for people in industrialized countries."

Which I interpret to mean the Tsimane with ApoE4 who had brain affecting infections were better at resisting the infection and thus better at retaining mental faculties than non-ApoE4.

Or did I totally miss what you were asking?
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Re: NY Times article on theory that parasitic infection may be reason APOE4 was once protective

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zombies and flamethrowers.....excellent image ;) down with the zombies!
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Re: NY Times article on theory that parasitic infection may be reason APOE4 was once protective

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Fiver wrote:zombies and flamethrowers.....excellent image ;) down with the zombies!
I was enjoying that too :D
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: NY Times article on theory that parasitic infection may be reason APOE4 was once protective

Post by Julie G »

Did anyone see the lengthy piece that Sanjay Gupta/CNN did on the Tsimane last night? You can see an overview here. Apparently, they've been found to have the healthiest hearts in the world, a title previously held by Japanese women. As Brian mentions above, they are hunter-gatherers (who engage in a bit of farming) with a heavily carb-based diet (70%): yucca, rice, corn and plantains are staples. They eat animal protein (15%); anything they can catch with bows and arrows- small prey, fowl, fish, even monkeys. They didn't mention their sources of fat (15%), but I would assume that it's associated with the animals they eat and coconuts given the tropical climate. They have no loneliness and a very tight social community. They're very active and rarely sit. There is no obesity and intermittent fasting is de rigueur due to food shortages. They go to sleep when it's dark and wake with the sun. They live in dirt-floor huts and are intimately familiar with the earth and water around them. Almost all of them have parasitic infections; giardia, hookworm or roundworm. Researchers suspect that these infections, in addition to protecting them from dementia, also protect their hearts.
Nearly everyone who lives there has some sort of parasitic infection such as hookworm, roundworm or giardia, according to the Lancet article. In a sense, the Tsimane cohabitate with these parasites most of their lives. Yes, that sounds disgusting, but keep in mind, it is how we humans lived for nearly all of our existence. And given that so many chronic diseases, including heart disease, are often ignited or worsened by our own immune systems, it is possible that the parasites in the bodies of the Tsimane help regulate their immune systems and protect their hearts. Now, I realize you are probably not going to go out and purposely get a parasite infection anytime soon, but the lesson here is that our self-imposed hygienic bubbles may actually be doing us more harm than we realize. Those with the healthiest hearts in the world aren't afraid to get a little dirty.
Apparently, they have fairly short lifespans due to animal and snake attacks, child birth and infection, but they are very healthy until the day they die. They have no healthcare system.
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