Genetic modifiers of the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) response

摘要 过量的铁（Fe）沉积与阿尔茨海默病（AD）有关。坚持地中海- DASH饮食干预神经退行性延迟（MIND）饮食模式可能会降低认知功能障碍的发生率。 降低AD的风险。MIND的膳食铁含量也相对较低，并富含抗氧化剂和铁螯合剂 植物营养素，反过来，可以防止铁诱导的神经毒性。膳食铁与 生物水平部分是由于饮食测量误差、补偿机制、健康状况和遗传 因素遗传因素可以作为工具来理解的机制之间的关系 MIND和AD，特别是坚持这种饮食的人。全基因组关联研究已 与外周铁相关的基因座仅部分与脑定量 易感性图（QSM）-Fe;与全身和大脑Fe的独特调节一致。是否这些 与直接测量死后脑铁相关的位点尚不清楚。 R 01 AG 065398利用第一个MIND试验以及现有的基于社区和人群的数据， 研究AD易感性的遗传差异和选择营养代谢如何改变对 主意了本补充将R 01扩展到Fe，并将是第一个i）调查 外周铁，脑QSM-Fe和死后脑铁和ii）测试的假设，参与者与 遗传推断的Fe失调在坚持MIND时受益最大， 较低的磁化率曲线。我们的研究将为MIND可能发挥的作用提供机械的见解， 减缓认知下降归因于铁，也将通知实施MIND的最佳 有效性

ABSTRACT Excess iron (Fe) deposition has been implicated in Alzheimer's disease (AD). Adherence to the Mediterranean- DASH Diet Intervention for Neurodegenerative Delay (MIND) dietary pattern may reduce the rate of cognitive decline and risk of AD. MIND is also relatively low in dietary Fe and rich in antioxidant and Fe-chelating phytonutrients that, in turn, may protect against Fe-induced neurotoxicity. Dietary Fe poorly correlates with biological levels partly due to diet measurement error, compensatory mechanisms, health status and genetic factors. Genetic factors can serve as tools to understand mechanisms underlying the relationship between MIND and AD and who especially benefit when adhering to this diet. Genome-wide association studies have identified loci correlated with peripheral Fe that only partly overlap with those identified for brain quantitative susceptibility mapping (QSM)-Fe; consistent with unique regulation of systemic and brain Fe. Whether these loci associate with directly measured postmortem brain Fe is unclear. R01AG065398 leverages the first MIND trial as well as existing community- and population-based data, to examine how genetic differences in AD predisposition and select nutrient metabolism modify the response to MIND. This Supplement extends this R01 to Fe and will be the first to i) investigate the genetic architecture of peripheral Fe, brain QSM-Fe and postmortem brain Fe and ii) test the hypothesis that participants with genetically inferred Fe dysregulation benefit the most when adhering to MIND compared to participants with lower susceptibility profiles. Our research will provide mechanistic insights into the role that MIND may play in slowing cognitive decline attributed to Fe and will also inform the implementation of MIND for optimal effectiveness.