Journal Article

DZNE-2025-00672

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png An Improved Method for Sampling and Quantitative Protein Analytics of Cerebrospinal Fluid of Individual Mice.

Lourbopoulos, A. ; Müller, S. A.DZNE* ; Jocher, G.DZNE* ; Wick, M. ; Plesnila, N. ; Lichtenthaler, S. F. (Last author)DZNE*

2025
The American Society for Biochemistry and Molecular Biology Bethesda, Md.

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Please use a persistent id in citations: doi:10.1016/j.mcpro.2025.100958

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.

Keyword(s): Animals (MeSH) ; Mice (MeSH) ; Proteomics: methods (MeSH) ; Alzheimer Disease: cerebrospinal fluid (MeSH) ; Cerebrospinal Fluid Proteins (MeSH) ; Proteome: metabolism (MeSH) ; Mice, Inbred C57BL (MeSH) ; Disease Models, Animal (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Mice, Transgenic (MeSH) ; Neurofilament Proteins: cerebrospinal fluid (MeSH) ; CSF collection ; aging ; cerebrospinal fluid ; method ; mouse ; neurodegeneration ; quantitative proteomics ; trauma ; Cerebrospinal Fluid Proteins ; Proteome ; Biomarkers ; Neurofilament Proteins ; neurofilament protein L

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Contributing Institute(s):

1. Neuroproteomics (AG Lichtenthaler)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2025

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Database coverage:
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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Müller, S. A.DZNE* ; Lichtenthaler, S.DZNE*
Dataset: Quantitative proteomics of CSF from the Alzheimer's disease mouse model 5xFAD
PRoteomics IDEntifications Database (2025)2025   Fulltext BibTeX | EndNote: XML, Text | RIS

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Müller, S. A.DZNE* ; Lichtenthaler, S.DZNE*
Dataset: Mouse CSF analysis of 3, 6, and 12 months old mice in comparison to human CSF
PRoteomics IDEntifications Database (2025)2025   Fulltext BibTeX | EndNote: XML, Text | RIS

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