APOE4 was the ancestral human genotype and is associated with a greater or heightened immune response compared to later genotypes.

“the history of the apoe4 alleles and to learn that apoe4 was the ancestral genotype um ... the apoe gene apoe protein um obviously involved is an apple protein so it's involved in uh lipid trafficking in the body but it's also um associated with immune function and inflammation and originally as humans you know maybe came down from the trees for one of a better phrase um as we were exposed to a new and greater number of insults um with the the original quote unquote original human apoe a genotype was apoe4 and it had it it compared to the others which came along later is often associated with a greater or heightened immune response in in certain settings”