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Plate IV.41 · Publications

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

Article in Cell, April 2026.

Diabetes, Children, Risk

  1. Jakob Maximilian Bader
  2. Christine Makarov
  3. Sabrina Richter
  4. Maximilian Thomas Strauss
  5. Friederike Held
  6. Maria Wahle
  7. Michael Baggio Lorenz
  8. Lara Pöschl
  9. Patricia Skowronek
  10. Marvin Thielert
  11. Achim Berthele
  12. Wen-Feng Zeng
  13. Constantin Ammar
  14. Isabell Bludau
  15. Benjamin Schubert
  16. Fabian J. Theis
  17. Christiane Gasperi
  18. Bernhard Hemmer
  19. Matthias Mann

Abstract

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.

Cite

@article{bader2026large,
  title = {{Large-scale proteomics across neurological disorders uncovers biomarker panel and targets in multiple sclerosis}},
  author = {Bader, Jakob Maximilian and Makarov, Christine and Richter, Sabrina and Strauss, Maximilian Thomas and Held, Friederike and Wahle, Maria and Lorenz, Michael Baggio and Pöschl, Lara and Skowronek, Patricia and Thielert, Marvin and Berthele, Achim and Zeng, Wen-Feng and Ammar, Constantin and Bludau, Isabell and Schubert, Benjamin and Theis, Fabian J. and Gasperi, Christiane and Hemmer, Bernhard and Mann, Matthias},
  journal = {Cell},
  publisher = {Elsevier BV},
  year = {2026},
  month = apr,
  doi = {10.1016/j.cell.2026.01.017},
  url = {https://doi.org/10.1016/j.cell.2026.01.017},
  pmid = {41747728}
}
.bib file