Notably, our results suggest that the mechanisms of HDL deficiency in APOE4 carriers vs. non-carriers are different, highlighting the need for further research on HDL metabolism and function in APOE genotyped individuals to elucidate the potential precision medicine-based approaches to improve the HDL functionality in individuals at risk for Alzheimer’s disease tailored to their APOE genotype. Here, APOE is linked to Alzheimer disease.