Objective: To identify molecular correlates of primary angiitis of the central nervous system (PACNS) through proteomic analysis of cerebrospinal fluid (CSF) from a biopsy-proven patient cohort. Methods: Using mass spectrometry, the CSF proteome of biopsy-proven PACNS patients (n=8) was quantitatively compared to CSF from individuals with non-inflammatory conditions (n=11). Significantly enriched molecular pathways were identified using a gene ontology workflow, and high confidence hits within enriched pathways (fold change >1.5 and concordant Benjamini-Hochberg-adjusted p-value <0.05 on DeSeq and t-test) were identified as differentially regulated proteins. Results: Compared to non-inflammatory controls, 283 proteins were differentially expressed in PACNS patient CSF, with significant enrichment of the complement cascade pathway (C4-binding protein, CD55, CD59, properdin, complement C5, complement C8 and complement C9) and neural cell adhesion molecules. A subset of clinically relevant findings was validated by western blot and commercial ELISA. Conclusions: In this exploratory study we found evidence of deregulation of the alternative complement cascade in CSF from biopsy-proven PACNS as compared to non-inflammatory controls. More specifically, several regulators of the C3 and C5 convertases and components of the terminal cascade were significantly altered. These preliminary findings shed light on a previously unappreciated similarity between PACNS and systemic vasculitides, especially Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis. The therapeutic implications of this common biology, and the diagnostic and/or therapeutic utility of individual proteomic findings warrant validation in larger cohorts.