The evolutionary pressure for ApoE3 and ApoE2 variants is unclear, as individuals were not living long enough to benefit from Alzheimer's risk reduction.

“it's always been confusing to me why there was any evolutionary pressure to create variants of e3 and e2 because the the best of my reading is that the e3 showed up about 50 000 years ago and e2 showed up about 10 000 years ago and again from a functional standpoint ten thousand fifty thousand and a hundred thousand are basically the same nobody was really living long enough to recoup the benefit of alzheimer's disease risk reduction going from three hundred 000 years ago to 50 to 10 000”