Large-scale proteomics across neurological disorders uncovers biomarker panel and targets in multiple sclerosis
Summary
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 di
Content
# Large-scale proteomics across neurological disorders uncovers biomarker panel and targets in multiple sclerosis
*Published: 2026 Apr 2*
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.
DOI: 10.1016/j.cell.2026.01.017