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

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 i...

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Autori principali: Bader, Jakob Maximilian (Autore) , Makarov, Christine (Autore) , Richter, Sabrina (Autore) , Strauss, Maximilian Thomas (Autore) , Held, Friederike (Autore) , Wahle, Maria (Autore) , Lorenz, Michael Baggio (Autore) , Pöschl, Lara (Autore) , Skowronek, Patricia (Autore) , Thielert, Marvin (Autore) , Berthele, Achim (Autore) , Zeng, Wen-Feng (Autore) , Ammar, Constantin (Autore) , Bludau, Isabell (Autore) , Schubert, Benjamin (Autore) , Theis, Fabian J. (Autore) , Gasperi, Christiane (Autore) , Hemmer, Bernhard (Autore) , Mann, Matthias (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: 2 April 2026
In: Cell
Year: 2026, Volume: 189, Fascicolo: 7, Pages: 2128-2147
ISSN:1097-4172
DOI:10.1016/j.cell.2026.01.017
Accesso online:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.cell.2026.01.017
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867426001042
Testo
Note sull'autore:Jakob Maximilian Bader, Christine Makarov, Sabrina Richter, Maximilian Thomas Strauss, Friederike Held, Maria Wahle, Michael Baggio Lorenz, Lara Pöschl, Patricia Skowronek, Marvin Thielert, Achim Berthele, Wen-Feng Zeng, Constantin Ammar, Isabell Bludau, Benjamin Schubert, Fabian J. Theis, Christiane Gasperi, Bernhard Hemmer, and Matthias Mann
Descrizione
Riassunto: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.
Descrizione del documento:Gesehen am 26.08.2026
Descrizione fisica:Online Resource
ISSN:1097-4172
DOI:10.1016/j.cell.2026.01.017

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