posted on 2019-01-31, 00:00authored byLoïc Dayon, Ornella Cominetti, Jérôme Wojcik, Antonio Núñez Galindo, Aikaterini Oikonomidi, Hugues Henry, Eugenia Migliavacca, Martin Kussmann, Gene L. Bowman, Julius Popp
The systems-level
relationship between the proteomes of cerebrospinal
fluid (CSF) and plasma has not been comprehensively described so far.
Recently developed shotgun proteomic workflows allow for deeper characterization
of the proteomes from body fluids in much larger sample size. We deployed
state-of-the-art mass spectrometry-based proteomics in paired CSF
and plasma samples volunteered by 120 elders with and without cognitive
impairment to comprehensively characterize and examine compartmental
proteome differences and relationships between both body fluids. We
further assessed the influence of blood–brain barrier (BBB)
integrity and tested the hypothesis that BBB breakdown can be identified
from CSF and plasma proteome alterations in nondemented elders. We
quantified 790 proteins in CSF and 422 proteins in plasma, and 255
of the proteins were identified in both compartments. Pearson’s
statistics determined 28 proteins with associated levels between CSF
and plasma. BBB integrity as defined with the CSF/serum albumin index
influenced 76 CSF/plasma protein ratios. In least absolute shrinkage
and selection operator models, CSF and plasma proteins improved identification
of BBB impairment. In conclusion, we provide here a first comprehensive
draft map of interacting human CSF and plasma proteomes, in view of
their complex and dynamic compositions, and influence of the BBB.