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Bader, J.M.* ; Makarov, C.* ; Richter, S. ; Strauss, M.T.* ; Held, F.* ; Wahle, M.* ; Lorenz, M.B.* ; Pöschl, L.* ; Skowronek, P.* ; Thielert, M.* ; Berthele, A.* ; Zeng, W.F.* ; Ammar, C.* ; Bludau, I.* ; Schubert, B. ; Theis, F.J. ; Gasperi, C.* ; Hemmer, B.* ; Mann, M.*

Large-scale proteomics across neurological disorders uncovers biomarker panel and targets in multiple sclerosis.

Cell 189, 2128-2147.e25 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Cerebrospinal fluid (CSF) is central to neurological diagnostics, yet biomarkers are lacking for many clinical needs. To enable its large-scale proteomic characterization, we developed a high-throughput mass spectrometry workflow quantifying approximately 1,500 proteins per CSF sample across 5,000 individuals, covering a spectrum of neurological disorders. This revealed proteomic alterations associated with blood-CSF barrier impairment, age, and sex, enabling deconvolution of shared and disease-specific signatures. We then focused on multiple sclerosis (MS), using an improved analytical technology that quantified 2,100 proteins per sample. From these data, we derived a 22-protein panel that distinguished MS from related inflammatory diseases and outperformed established markers in challenging cases. A targeted mass spectrometry assay using isotope-labeled standards validated this panel in an independent cohort, offering a clinically compatible format. Additionally, we highlight proteins of therapeutic interest and demonstrate proteome-based staging of individuals along the relapsing-progressive MS spectrum, which correlates with clinical outcomes.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Biomarkers ; Blood Csf Barrier Impairment ; Cerebrospinal Fluid ; Multiple Sclerosis ; Oligoclonal Bands ; Proteomics ; Targeted Mass Spectrometry; Cerebrospinal-fluid; Ifn-gamma; Protein; Cells; Identification; Diagnosis; Revisions; Brain; Light
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Journal Cell
Quellenangaben Volume: 189, Issue: 7, Pages: 2128-2147.e25 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants (German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology