Human cerebrospinal fluid contains diverse lipoprotein subspecies enriched in proteins implicated in central nervous system health

Nathaniel J. Merrill, W. Sean Davidson, Yi He, Ivo Díaz Ludovico, Snigdha Sarkar, Madelyn R. Berger, Jason E. McDermott, Linda J. Van Eldik, Donna M. Wilcock, Matthew E. Monroe, Jennifer E. Kyle, Kimberley D. Bruce, Jay W. Heinecke, Tomas Vaisar, Jacob Raber, Joseph F. Quinn, John T. Melchior

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Article numbereadi5571
JournalScience advances
Volume9
Issue number35
DOIs
StatePublished - 2023

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ASJC Scopus subject areas

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