Dr. Jeffrey Gladden explains how APOE4, an allele that helped early humans survive infections through stronger inflammation, became a liability in modern life. For tens of thousands of years it was protective. Now, without acute infectious threats, that same inflammatory response accelerates chronic disease.
Because with ApoE4, we know that there was a survival benefit to ApoE4. Everybody was ApoE4 for like 10, 20, 30,000 years ago, right? Because there was a survival benefit. And what was the survival benefit? Well, they mounted a greater inflammatory response to whatever they were facing, right? So you now have something that was beneficial in one context, right, where it's helping you to survive because you got an inflammatory response to kill off a bug that would have killed you otherwise. So that's helpful. But then later on, when you get into a world where that's less the case, now it's being activated by these other pathogens in a way that's accelerating another process, right? So it's a really interesting interplay between genetic survival timelines for survival. Like APOE4 was good for short-term survival, but not so great for long-term survival, right? So— Yes. It just depends on what challenge the organism's trying to overcome in the moment.
