Deep Dive on the Proteome of Human Cerebrospinal Fluid: A Valuable Data Resource for Biomarker Discovery and Missing Protein Identification

Cerebrospinal
fluid (CSF) is a body fluid of choice for biomarker
studies of brain disorders but remains relatively under-studied compared
with other biological fluids such as plasma, partly due to the more
invasive means of its sample collection. The present study establishes
an in-depth CSF proteome through the analysis of a unique CSF sample
from a pool of donors. After immunoaffinity depletion, the CSF sample
was fractionated using off-gel electrophoresis and analyzed with liquid
chromatography tandem mass spectrometry (MS) using the latest generation
of hybrid Orbitrap mass spectrometers. The shotgun proteomic analysis
allowed the identification of 20 689 peptides mapping on 3379
proteins. To the best of our knowledge, the obtained data set constitutes
the largest CSF proteome published so far. Among the CSF proteins
identified, 34% correspond to genes whose transcripts are highly expressed
in brain according to the Human Protein Atlas. The principal Alzheimer’s
disease biomarkers (e.g., tau protein, amyloid-β, apolipoprotein
E, and neurogranin) were detected. Importantly, our data set significantly
contributes to the Chromosome-centric Human Proteome Project (C-HPP),
and 12 proteins considered as missing are proposed for validation
in accordance with the HPP guidelines. Of these 12 proteins, 8 proteins
are based on 2 to 6 uniquely mapping peptides from this CSF analysis,
and 4 match a new peptide with a “stranded” single peptide
in PeptideAtlas from previous CSF studies. The MS proteomic data are
available to the ProteomeXchange Consortium (http://www.proteomexchange.org/) with the data set identifier PXD009646.