Citations 1
A shared injury–homeostasis gradient in the human CSF proteome across neurological disease
Mansouri, Alireza , Mikolajewicz, Nicholas , Riviere-Cazaux, Cécile , Tuohy, Kyle , Kumar, Rahul , Miller, Alexandra, Ahluwalia, Manmeet S. , Bettegowda, Chetan , Burns, Terry, Mansouri, Alireza , Ahluwalia, Manmeet S , Kumar, Rahul , Bettegowda, Chetan , Tuohy, Kyle , Ranganathan, Sruthi , Boutros, Paul C. , Kislinger, Thomas
No container title available | August 11, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Cerebrospinal fluid (CSF) is the biofluid most proximal to the central nervous system (CNS), yet its proteomic organization across neurological disease remains unresolved. We assembled a meta-atlas of 35 CSF proteomic datasets (2016–2026) comprising 10,560 quality-controlled samples spanning neurodegenerative, neuroinflammatory, neuro-oncological, infectious and structural-injury contexts. Meta-analysis of cross-cohort detection defined a 747-protein core mass-spectrometry-accessible CSF proteome that generalizes to held-out cohorts. We derived thirteen consensus meta-programs that transfer across independent cohorts and span the major neural, barrier, immune and plasma compartments. Unexpectedly, these programs are dominated by a single axis of variation opposing complement- and plasma-associated inflammation against neuronal-synaptic homeostasis. This injury–homeostasis axis is diagnosis-spanning and tracks clinical severity and disease activity across diverse neurological conditions. We show that a two-protein C5–NRCAM model can approximate the injury–homeostasis axis, bridging deep proteomic profiling toward bedside assessment.