PNNL

Abstract

Lipoproteins in cerebral spinal fluid of the central nervous system resemble plasma high-density lipoproteins (HDL),), which are a compositionally and structurally diverse spectrum of nanoparticles with a wide range of functions. Whether CSF lipoproteins exhibit similar heterogeneity is poorly understood because they are present at 10-fold lower concentrations than plasma HDL. To better define the diversity of CSF-Lps we developed a sensitive fluorescent technology to characterize lipoprotein subspecies in small volumes of human CSF. Curve fitting identified 10 distinct sizes 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 identified in plasma HDL. The majority of the proteins were enriched in specific subpopulations of CSF lipoproteins. Computational analyses suggested that (indicated) different combinations of these proteins form functional hubs that are important for processes such as wound healing, inflammation, immune response and neuron generation and development. Our study demonstrates that CSF-Lps subspecies exist that contain compositional signatures related to CNS health.