INTRODUCTION High-fat diets increase risk for Alzheimer's disease, but individuals with the risk gene APOE ε4 (E4) paradoxically have improved memory soon after high fat feeding. Little is known about how dietary lipids affect CNS lipids, especially in older adults. OBJECTIVES We analyzed the lipidomic signature of cerebrospinal fluid (CSF) in older adults who underwent both a saline and TG infusion. We further analyzed these data by E4 carrier status. METHODS Older adults (n = 21, age 67.7 ± 8.6) underwent a 5-h TG and saline infusion on different days in random crossover design; lumbar CSF was collected at the end of the infusion. Lipids were extracted using dichloromethane/methanol and 13 classes of lipids analyzed using the Lipidyzer platform consisting of an AB Sciex 5500 MS/MS QTraps system equipped with a SelexION for differential mobility spectrometry (DMS). Multiple reaction monitoring was used to target and quantify 1070 lipids in positive and negative ionization modes with and without DMS. RESULTS The TG infusion increased total lipids in the CSF, including the appearance of more lipids at the detection limit in the TG samples compared to saline (Chi square p < 0.0001). The infusion increased the total level of diacylglycerols and lysophosphatidylcholines and reduced dihydroceramides. Of the possible 1070 lipids detectable, we found 348 after saline and 365 after TG infusion. Analysis using MetaboAnalyst revealed 11 specific lipids that changed; five of these lipids decreased after TG infusion, and four of them differed by E4 status, but none differed by cognitive diagnosis or sex. CONCLUSION These results in older adults show that blood lipids affect lipid profiles in CSF and such profiles are modified by APOE status. This suggests that how the CNS handles lipids may be important in the AD phenotype.

中文翻译：

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脑脊液脂质组学：静脉输注甘油三酯和 apoE 状态的影响。

引言 高脂肪饮食会增加患阿尔茨海默病的风险，但具有危险基因 APOE ε4 (E4) 的个体在高脂肪饮食后记忆力却很快得到改善。人们对膳食脂质如何影响中枢神经系统脂质（尤其是老年人）知之甚少。目的 我们分析了接受盐水和 TG 输注的老年人脑脊液 (CSF) 的脂质组学特征。我们通过 E4 运营商状态进一步分析了这些数据。方法 老年人（n = 21，年龄 67.7 ± 8.6）在随机交叉设计的不同日期接受 5 小时 TG 和生理盐水输注；输注结束时收集腰椎脑脊液。使用二氯甲烷/甲醇提取脂质，并使用 Lipidyzer 平台分析 13 类脂质，该平台由 AB Sciex 5500 MS/MS QTraps 系统组成，配备用于微分迁移谱 (DMS) 的 SelexION。多重反应监测用于在正电离和负电离模式下（使用和不使用 DMS）对 1070 种脂质进行靶向和定量。结果 与生理盐水相比，TG 输注增加了 CSF 中的总脂质，包括在 TG 样品中出现更多达到检测限的脂质（卡方 p < 0.0001）。输注增加了二酰甘油和溶血磷脂酰胆碱的总水平，并减少了二氢神经酰胺。在可能检测到的 1070 种脂质中，我们在盐水注射后发现了 348 种，在输注 TG 后发现了 365 种。使用 MetaboAnalyst 进行的分析揭示了 11 种特定脂质发生了变化；其中 5 种脂质在 TG 输注后下降，其中 4 种因 E4 状态而异，但没有因认知诊断或性别而异。结论 这些老年人的结果表明，血脂影响脑脊液中的脂质分布，并且这种分布会因 APOE 状态而改变。这表明中枢神经系统如何处理脂质可能对 AD 表型很重要。