The APOE protein isoform produced by an individual's genotype dictates the functionality of brain HDL particles and their ability to successfully transport cholesterol to neurons.

“So depending which of those genes you attack, your APOE protein is going to be constructed a little bit differently, which is going to affect its ability to function, whatever APOE is doing when it's stuck to a lipoprotein.”

The ApoE4 allele likely provided an evolutionary survival advantage against infectious diseases in ancestral environments, but this benefit is less relevant in modern, longer-lived populations.

“we know now that apoe4 women had a better chance of giving childbirth and protection from perpetual sepsis compared to non-e4 women in the slums of brazil or in certain areas in africa we know that based on studies that e4 confers some form of an advantage”