■鞘脂与神经变性和神经炎症有关。我们通过研究循环神经酰胺和鞘磷脂与脑磁共振成像(MRI)测量和脑损伤循环生物标志物的关联,评估了它们在亚临床脑病理学中的潜在作用。心血管健康研究(CHS)中的神经丝轻链(NfL)和神经胶质纤维酸性蛋白(GFAP),一个庞大而密集的老年人表型队列。
■对CHS参与者进行了两次脑部MRI检查,两次扫描之间平均为5年,2,116名参与者(平均年龄76岁;40%男性;25%APOEε4等位基因携带者)的两个时间点的结果均可用。我们测量了血浆样本中的8种神经酰胺和鞘磷脂,并检查了其与几种MRI的关联。包括白质高强度和心室大小的恶化,脑梗塞的数量,以及用定量方法测量脑萎缩的子集。我们还研究了鞘脂与血清NfL和GFAP的相关性。
■在完全调整的模型中,具有长(16碳)饱和脂肪酸的神经酰胺和鞘磷脂的血浆水平较高与血液中NfL水平较高相关[β=0.05,假发现率校正P(PFDR)=0.004和β=0.06,PFDR=<0.001,分别].相比之下,具有很长(20-和22-碳)饱和脂肪酸的鞘磷脂倾向于与循环NfL的水平呈负相关。在二级分析中,我们发现神经酰胺d18:1/20:0与性别之间存在相互作用(相互作用的P=<0.001),因此,神经酰胺d18:1/20:0与女性梗死的几率更高相关[OR=1.26(95CI:1.07,1.49),PFDR=0.03]。我们没有观察到与GFAP血液水平的任何关联,白质等级,心室分级,平均双侧海马体积,或大脑总体积。
■总的来说,我们的全面调查支持以下证据:神经酰胺和鞘磷脂与脑老化病理增加相关,且相关方向取决于附在鞘氨醇骨架上的脂肪酸.
UNASSIGNED: Sphingolipids are implicated in neurodegeneration and neuroinflammation. We assessed the potential role of circulating ceramides and sphingomyelins in subclinical brain pathology by investigating their association with brain magnetic resonance imaging (MRI) measures and circulating biomarkers of brain injury, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in the Cardiovascular Health Study (CHS), a large and intensively phenotyped cohort of older adults.
UNASSIGNED: Brain MRI was offered twice to CHS participants with a mean of 5 years between scans, and results were available from both time points in 2,116 participants (mean age 76 years; 40% male; and 25% APOE ε4 allele carriers). We measured 8 ceramide and
sphingomyelin species in plasma samples and examined the associations with several MRI, including worsening grades of white matter hyperintensities and ventricular size, number of brain infarcts, and measures of brain atrophy in a subset with quantitative measures. We also investigated the sphingolipid associations with serum NfL and GFAP.
UNASSIGNED: In the fully adjusted model, higher plasma levels of ceramides and sphingomyelins with a long (16-carbon) saturated fatty acid were associated with higher blood levels of NfL [β = 0.05, false-discovery rate corrected P (PFDR) = 0.004 and β = 0.06, PFDR = < 0.001, respectively]. In contrast, sphingomyelins with very long (20- and 22-carbon) saturated fatty acids tended to have an inverse association with levels of circulating NfL. In secondary analyses, we found an interaction between ceramide d18:1/20:0 and sex (P for interaction = <0.001), such that ceramide d18:1/20:0 associated with higher odds for infarcts in women [OR = 1.26 (95%CI: 1.07, 1.49), PFDR = 0.03]. We did not observe any associations with GFAP blood levels, white matter grade, ventricular grade, mean bilateral hippocampal volume, or total brain volume.
UNASSIGNED: Overall, our comprehensive investigation supports the evidence that ceramides and sphingomyelins are associated with increased aging brain pathology and that the direction of association depends on the fatty acid attached to the sphingosine backbone.