Interesting!

FWIW, APOE4 is a good example of antagonistic pleiotropy (good when you're of reproductive age - then very much not). For APOE4, it's higher intelligence, then susceptibility to AD. Given the way single-cell transcriptomics works (measuring mRNA in the cytosol — full explanation here). I would expect this to be quite different between young and old brains - there are large transcriptomic differences between young and old mouse brain tissue. I'm curious how many postmortem samples they had of reproductive age APOE4 carriers. I'd look at the methods section, but it's paywalled, and I'm not $32 interested (and Sci-Hub isn't getting me read-once access).

I'm also curious as to what those 'certain Nigerian populations' are doing to make APOE4 not matter(?) It could be as simple as the Nigerian expected lifespan being around 55 (which would definitely reduce late onset AD in the population) - or it could be something dietary like red palm oil (prevalent in the Nigerian diet similar to olive oil in Greece) which is high in tocotrienols. Like tocopherol, the other vitamin E, it’s an antioxidant — but it also has neuroprotective properties, and I think it’s in medical use for diabetic retinopathy (but the action there is more neuro-adjacent than directly protective).

At one point I thought I was probably APOE4, and along with phospholipids, I was taking tocotrienols. Turns out I’m not, but if you’re wondering why I dug into this area…

Oh, and speaking of antagonistic pleiotropy, I don’t know of a single one that works the other way (bad when of reproductive age, then good for aging). If there’s a bio person reading this who knows of one, I’d love to learn about it (please?)