Associations of single nucleotide polymorphisms (SNPs) of the MLXIPL lipid gene with Alzheimer’s (AD) and coronary heart disease (CHD) and potentially causal mediation effects of their risk factors, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), were examined in two samples of European ancestry from the US (22,712 individuals 587/2,608 AD/CHD cases) and the UK Biobank (UKB) (232,341 individuals; 809/15,269 AD/CHD cases). This evidence concerns the gene MLXIPL and coronary artery disorder.