Maryland Psychiatric Research Center, Department of Psychiatry, School of Medicine, University of Maryland, Baltimore, MD 21201, United States; Division of Biostatistics and Bioinformatics, Department of Epidemiology and Public Health, School of Medicine, University of Maryland, Baltimore, MD 21201, United States.
Maryland Psychiatric Research Center, Department of Psychiatry, School of Medicine, University of Maryland, Baltimore, MD 21201, United States.
Neurobiol Aging. 2024 Nov;143:41-52. doi: 10.1016/j.neurobiolaging.2024.08.005. Epub 2024 Aug 22.
Apolipoprotein E ε4 (APOE4) is a strong genetic risk factor of Alzheimer's disease and metabolic dysfunction. However, whether APOE4 and markers of metabolic dysfunction synergistically impact the deterioration of white matter (WM) integrity in older adults remains unknown. In the UK Biobank data, we conducted a multivariate analysis to investigate the interactions between APOE4 and 249 plasma metabolites (measured using nuclear magnetic resonance spectroscopy) with whole-brain WM integrity (measured by diffusion-weighted magnetic resonance imaging) in a cohort of 1917 older adults (aged 65.0-81.0 years; 52.4 % female). Although no main association was observed between either APOE4 or metabolites with WM integrity (adjusted P > 0.05), significant interactions between APOE4 and metabolites with WM integrity were identified. Among the examined metabolites, higher concentrations of low-density lipoprotein and very low-density lipoprotein were associated with a lower level of WM integrity (b=-0.12, CI=-0.14,-0.10) among APOE4 carriers. Conversely, among non-carriers, they were associated with a higher level of WM integrity (b=0.05, CI=0.04,0.07), demonstrating a significant moderation role of APOE4 (b =-0.18, CI=-0.20,-0.15, P<0.00001).
载脂蛋白 E ε4（APOE4）是阿尔茨海默病和代谢功能障碍的强烈遗传风险因素。然而，APOE4 与代谢功能障碍标志物是否协同影响老年人白质（WM）完整性的恶化尚不清楚。在英国生物库数据中，我们进行了多变量分析，以调查 APOE4 与 249 种血浆代谢物（使用核磁共振波谱法测量）与全脑 WM 完整性（通过扩散加权磁共振成像测量）之间在 1917 名老年人（年龄 65.0-81.0 岁；52.4%为女性）队列中的相互作用。尽管在 WM 完整性与 APOE4 或代谢物之间未观察到主要关联（调整后的 P > 0.05），但WM 完整性与 APOE4 和代谢物之间存在显著的相互作用。在检查的代谢物中，载脂蛋白 E4 携带者的 LDL 和 VLDL 浓度较高与 WM 完整性水平较低有关（b=-0.12，CI=-0.14，-0.10）。相反，在非携带者中，它们与 WM 完整性水平较高有关（b=0.05，CI=0.04，0.07），表明 APOE4 具有显著的调节作用（b=-0.18，CI=-0.20，-0.15，P<0.00001）。
