Personalized Nutrition for APOE4 carriers: mechanisms and biomarkers that can inform future trials

Abstract

AbstractCurrent studies suggest that the beneficial effects of increased polyunsaturated fat consumption (Mediterranean diet, fish consumption or long‐term DHA supplementation) on cognition are stronger in younger and middle aged APOE4 carriers. The efficacy of these nutritional interventions in APOE4 appears to wane with advancing age and cognitive disease. In addition, a recent systematic review revealed that ketogenic diets do not appear to have a beneficial effect on cognitive performance in APOE4 carriers compared to non‐carriers.In this talk, we focus on leading mechanisms of cerebral bioenergetic breakdown in the aging APOE4 brain that implicate neuroinflammation in several brain cell types including those of the blood‐brain barrier (BBB). We then address consequences of neuroinflammation and disturbed bioenergetics at the BBB on the delivery and brain metabolism of nutrients such as omega‐3s, nutrients and ketones. We provide examples of novel lipidomic biomarkers that can capture neuroinflammation in the Religious Order Study, DHA Brain Pilot Trial, and the ADCS DHA trial. Advances in brain imaging of polyunsaturated fatty acid brain uptake by PET are provided to obtain insights into APOE4 brain fatty acid consumption changes during the lifespan. Finally, we highlight how the ongoing PreventE4 trial is integrating measures of the gut microbiome to understand the effects of omega‐3 supplementation on the brain in individuals carrying the APOE4 allele and at risk for dementia.