2026/02/25 by Jakob M. Bader, Christine Makarov, Sabrina Richter +16 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Advanced Biosensing Techniques and Applications #Advanced Proteomics Techniques and Applications #Multiple Sclerosis Research Studies
paper · doi:10.1016/j.cell.2026.01.017
openalex publication_date 2026/02/25 · openalex created_date 2026/02/26 · openalex updated_date 2026/07/23
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.