Regarding the Frammingham study, the authors say "Since DNA was not collected at baseline in this cohort, it is possible that attrition mainly due to death might have altered the study population. Such alteration could lead to biased estimate if for example subjects with E4 allele were more likely to die than those without E4 allele." They also show that alcohol has a positive correlation with HDL and reduced ischemic stroke independent of E4. This cross-sectional study is suggesting correlations that are contrary to what almost all interventional studies show.
Considering their limitations, it could be that those with E4 who have other compensatory mechanisms to gain benefit from alcohol do in fact get benefits. I've come across studies (
example) that show alcohol increases only the HDL2 subfraction, which is the least protective, and potentially even negative. Still, the interventional studies are where I'd put my money, and they mostly suggest net neutral or negative
.The second study you linked concludes: "In conclusion, although analysis found that the presence of APOE ɛ4 allele eliminated any significant “protective” effect of moderate ethanol on cognitive risk, a number of other studies have found an opposite effect and our results are based on a relatively small number of ratios from just ten studies, leaving this question unsettled." Their "number of other studies" showing benefit show very little benefit, are comparatively under-powered, and are few compared to the number of studies suggesting negative outcomes.
I'd be curious to know if the benefits of a reduced cholesterol and saturated fat diet might reduce the risk risk of CVD and vascular dementia in those with ApoE4 enough for them enjoy alcohol in moderation, without significantly altering their risk. For personal motives, I sort of follow this reasoning for the time being, though I wouldn't suggest another person follow my advice. My main concern with drinking, and the reason I would cut back (I have) or stop completely, is that alcohol (actually acetaldehyde) is neurotoxic and ApoE4 seems to reduce neuronal plasticity and recovery from insult. I'd definitely avoid binge drinking, but perhaps also moderate drinking as it could lead to years of accumulating slight damage over time.