Williams DM, et al. – In this study, researchers determined if long-term circulating antioxidant exposure plays a role in Alzheimer disease (AD) etiology by testing the premise that AD risk would be lower in individuals with lifelong, genetically predicted increases in concentrations of four circulating antioxidants that are modifiable by diet. To that end, they performed two-sample Mendelian randomization analyses, and investigated single-nucleotide polymorphisms (SNPs) that determine variation in circulating ascorbate (vitamin C), β-carotene, retinol (vitamin A), and urate by analyzing published genetic-association studies. Using data of a genome-wide association study of late-onset AD cases and controls (n=17,008 and 37,154, respectively), they extracted statistics for genotype associations with AD risk for each set of SNP data. According to findings, no lowered risk of AD was observed in association with higher exposure to ascorbate, β-carotene, retinol, or urate. Replication Mendelian randomization studies could assess this further, providing larger AD case-control samples and, ideally, using additional variants to instrument each exposure.