BACKGROUND: In cerebrospinal fluid (CSF), which is a rich source of biomarkers 
for neurological diseases, identification of biomarkers requires methods that 
allow reproducible detection of low abundance proteins. It is therefore crucial 
to decrease dynamic range and improve assessment of protein abundance.
RESULTS: We applied LC-MS/MS to compare the performance of two CSF enrichment 
techniques that immunodeplete either albumin alone (IgYHSA) or 14 high-abundance 
proteins (IgY14). In order to estimate dynamic range of proteins identified, we 
measured protein abundance with APEX spectral counting method.Both 
immunodepletion methods improved the number of low-abundance proteins detected 
(3-fold for IgYHSA, 4-fold for IgY14). The 10 most abundant proteins following 
immunodepletion accounted for 41% (IgY14) and 46% (IgYHSA) of CSF protein 
content, whereas they accounted for 64% in non-depleted samples, thus 
demonstrating significant enrichment of low-abundance proteins. Defined 
proteomics experiment metrics showed overall good reproducibility of the two 
immunodepletion methods and MS analysis. Moreover, offline peptide fractionation 
in IgYHSA sample allowed a 4-fold increase of proteins identified (520 vs. 131 
without fractionation), without hindering reproducibility.
CONCLUSIONS: The novelty of this study was to show the advantages and drawbacks 
of these methods side-to-side. Taking into account the improved detection and 
potential loss of non-target proteins following extensive immunodepletion, it is 
concluded that both depletion methods combined with spectral counting may be of 
interest before further fractionation, when searching for CSF biomarkers. 
According to the reliable identification and quantitation obtained with APEX 
algorithm, it may be considered as a cheap and quick alternative to study sample 
proteomic content.