Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
Center for Lipid and Arteriosclerosis Science, Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237, USA.
Sci Adv. 2023 Sep;9(35):eadi5571. doi: 10.1126/sciadv.adi5571. Epub 2023 Aug 30.
Lipoproteins in cerebrospinal fluid (CSF) of the central nervous system (CNS) resemble plasma high-density lipoproteins (HDLs), which are a compositionally and structurally diverse spectrum of nanoparticles with pleiotropic functionality. Whether CSF lipoproteins (CSF-Lps) exhibit similar heterogeneity is poorly understood because they are present at 100-fold lower concentrations than plasma HDL. To investigate the diversity of CSF-Lps, we developed a sensitive fluorescent technology to characterize lipoprotein subspecies in small volumes of human CSF. We identified 10 distinctly sized populations of CSF-Lps, most of which were larger than plasma HDL. Mass spectrometric analysis identified 303 proteins across the populations, over half of which have not been reported in plasma HDL. Computational analysis revealed that CSF-Lps are enriched in proteins important for wound healing, inflammation, immune response, and both neuron generation and development. Network analysis indicated that different subpopulations of CSF-Lps contain unique combinations of these proteins. Our study demonstrates that CSF-Lp subspecies likely exist that contain compositional signatures related to CNS health.
中枢神经系统（CNS）脑脊液（CSF）中的脂蛋白与血浆高密度脂蛋白（HDL）相似，是一组组成和结构多样的纳米颗粒，具有多种功能。由于 CSF 脂蛋白（CSF-Lps）的浓度比血浆 HDL 低 100 倍，因此它们是否表现出相似的异质性尚不清楚。为了研究 CSF-Lps 的多样性，我们开发了一种灵敏的荧光技术来表征小体积人 CSF 中的脂蛋白亚种。我们鉴定出 10 种明显大小的 CSF-Lps 群体，其中大多数大于血浆 HDL。质谱分析鉴定出跨越这些群体的 303 种蛋白质，其中一半以上在血浆 HDL 中没有报道。计算分析表明，CSF-Lps 富含对伤口愈合、炎症、免疫反应以及神经元生成和发育都很重要的蛋白质。网络分析表明，CSF-Lps 的不同亚群含有这些蛋白质的独特组合。我们的研究表明，可能存在 CSF-Lp 亚种，其中包含与 CNS 健康相关的组成特征。
