My understanding of one guess around e.g. annual flu shots is not so much protection from infection as frequent stimulation of the immune system being beneficial in particular for Apoe4 carriers.
E.g. from p. 329 of Lieberman's Exercised:
> Although Westerners who carry the two copies of a gene called Apoe4 (a protein that transports fats in the bloodstream) are three to fifteen times more likely to get Alzheimer's in old age, elderly Tsimane with the same ApoE4 gene are less likely to show declines in cognitive performance if they suffer from many infections.
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I have heard something similar about ApoE4 carriers in Nigeria though don't have a source on hand. Basically a lot of variations of the hygiene hypothesis and possibly compatible with "angry immune cells". Definitely not a "mystery solved" though.
E.g. from p. 329 of Lieberman's Exercised:
> Although Westerners who carry the two copies of a gene called Apoe4 (a protein that transports fats in the bloodstream) are three to fifteen times more likely to get Alzheimer's in old age, elderly Tsimane with the same ApoE4 gene are less likely to show declines in cognitive performance if they suffer from many infections.
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I have heard something similar about ApoE4 carriers in Nigeria though don't have a source on hand. Basically a lot of variations of the hygiene hypothesis and possibly compatible with "angry immune cells". Definitely not a "mystery solved" though.