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@ARTICLE{Lourbopoulos:279042,
author = {Lourbopoulos, Athanasios and Müller, Stephan A and Jocher,
Georg and Wick, Manfred and Plesnila, Nikolaus and
Lichtenthaler, Stefan F},
title = {{A}n {I}mproved {M}ethod for {S}ampling and {Q}uantitative
{P}rotein {A}nalytics of {C}erebrospinal {F}luid of
{I}ndividual {M}ice.},
journal = {Molecular $\&$ cellular proteomics},
volume = {24},
number = {5},
issn = {1535-9476},
address = {Bethesda, Md.},
publisher = {The American Society for Biochemistry and Molecular
Biology},
reportid = {DZNE-2025-00672},
pages = {100958},
year = {2025},
abstract = {The mouse is the species most commonly used in preclinical
research, but protein analytics of murine cerebrospinal
fluid (CSF) remains challenging because of low sample
volumes (often <10 μl) and frequent contaminations with
blood. We developed an improved CSF sampling method that
allows routine collection of larger volumes (20-30 μl) of
pure CSF from individual mice, enabling multiple protein
analytical assays from a single sample. Based on cell counts
and hemoglobin ELISAs, we provide an easy quality control
workflow for obtaining cell- and blood-free murine CSF.
Through mass spectrometry-based proteomics using an
absolutely quantified external standard, we estimated
concentrations for hundreds of mouse CSF proteins. While
repeated CSF sampling from the same mouse was possible, it
induced CSF proteome changes. Applying the improved method,
we found that the mouse CSF proteome remains largely stable
over time in wild-type mice, but that amyloid pathology in
the 5xFAD mouse model of Alzheimer's disease massively
changes the CSF proteome. Neurofilament light chain and
TREM2, markers of neurodegeneration and activated microglia,
respectively, were strongly upregulated and validated using
immunoassays. In conclusion, our refined murine CSF
collection method overcomes previous limitations, allowing
multiple quantitative protein analyses for applications in
biomedicine.},
keywords = {Animals / Mice / Proteomics: methods / Alzheimer Disease:
cerebrospinal fluid / Cerebrospinal Fluid Proteins /
Proteome: metabolism / Mice, Inbred C57BL / Disease Models,
Animal / Biomarkers: cerebrospinal fluid / Mice, Transgenic
/ Neurofilament Proteins: cerebrospinal fluid / CSF
collection (Other) / aging (Other) / cerebrospinal fluid
(Other) / method (Other) / mouse (Other) / neurodegeneration
(Other) / quantitative proteomics (Other) / trauma (Other) /
Cerebrospinal Fluid Proteins (NLM Chemicals) / Proteome (NLM
Chemicals) / Biomarkers (NLM Chemicals) / Neurofilament
Proteins (NLM Chemicals) / neurofilament protein L (NLM
Chemicals)},
cin = {AG Lichtenthaler},
ddc = {610},
cid = {I:(DE-2719)1110006},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40157722},
pmc = {pmc:PMC12090247},
doi = {10.1016/j.mcpro.2025.100958},
url = {https://pub.dzne.de/record/279042},
}