White Americans are largely of European descent,5 and are the largest group in the US population and dementia trials.6 Previous studies in Europe show that APOE ε4 prevalence is lower among Southern, than among Northen Europeans with AD.7,8 Europeans and European Americans from these regions can be differentiated consistently in a genome-wide single nucleotide polymorphism panel.9 In this manuscript, we tested whether the prevalence of APOE ε4 and its association with brain health outcomes differ between Americans of Northern (AmEuro-N) and Southern European descent (AmEuro-S). Here, APOE is linked to dementia.