Paul Saladino· MD
throughout our whole evolution 804 has probably been protective but there's a strong argument that those who are metabolically healthy do not have problems with apoe4
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The evidence is convergent. Multiple independent sources reach the same conclusion, the underlying mechanism is well-characterized, and even the field's most cautious voices treat it as worth doing.
throughout our whole evolution 804 has probably been protective but there's a strong argument that those who are metabolically healthy do not have problems with apoe4
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historically apoe4 was the variant that prehominids and humans had for hundreds of thousands of years
this genotype was associated with protection from parasitic infections in the brain which would have been far more to our advantage a hundred thousand years ago fifty thousand years ago ten thousand years ago than the downside of alzheimer's disease in your seventies or eighties
Apoe is a gene that today doesn't seem to serve much of a purpose all it seems to do is increase your risk of alzheimer's disease and even increase your risk of cardiovascular disease independent of that um there are three isoforms the two three four type and it's this fourth type that's high risk so you can argue how in the world does this gene exist and of course the answer is evolution wasn't really thinking about alzheimer's disease so therefore there must have been some benefit of it and of course we now know there is right this this genotype was associated with protection from parasitic infections in the brain which would have been far more to our advantage a hundred thousand years ago fifty thousand years ago ten thousand years ago than the downside of alzheimer's disease in your seventies or eighties
APOE4 which basically was the only apoe isoform we had until what 200 000 years ago yeah something like that I think yeah and it offered remarkable protection against infections and of course it's only today a with our longer life but B I would argue with all of the insults that come with our longer life that APO E4 is such a predisposing factor to both cardiovascular and neurodegenerative risk factor