Evolution of circulating metabolites through lifespan according to gender and APOE

Background There is increasing interest in blood-based metabolic biomarkers for Alzheimer’s disease (AD). Studies show consistently that at branched chain amino acids (BCAAs) and a large scale of lipids are changed patients with AD. Little known how these metabolites associate to age, genes apolipoprotein E (APOE). This study aims over the lifespan determine influence sex APOE. Method We conducted this UK Biobank, prospective cohort 459,227 subjects extensive genotypic phenotypic data. Using Nightingale nuclear magnetic resonance technology, 249 (165 directly measured 84 derived measures) have been determined blood 118,071 participants. used mixed-effect models effect APOE on metabolite levels adjust lifestyle factors medication. Results APOE*4 major determinant total 216 platform using FDR < 0.05. find 41 were also associated dementia population 60+ years old. Also, APOE*2 226 (FDR<0.05) including metabolites. Concerning gender differences, significant differences found Overall, we interaction between age^2 valine BCAA. When stratifying gender, most concentrations remain stable age men. For acids, observed decreased concentration level me. females, increase reaching plateau around 55 Conclusion shows AD by In women, women up until menopause.