AUTHOR=Ruland Tillmann , Wolbert Jolien , Gottschalk Michael G. , König Simone , Schulte-Mecklenbeck Andreas , Minnerup Jens , Meuth Sven G. , Groß Catharina C. , Wiendl Heinz , Meyer zu Hörste Gerd TITLE=Cerebrospinal Fluid Concentrations of Neuronal Proteins Are Reduced in Primary Angiitis of the Central Nervous System JOURNAL=Frontiers in Neurology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.00407 DOI=10.3389/fneur.2018.00407 ISSN=1664-2295 ABSTRACT=

Primary angiitis of the central nervous system (PACNS) is a rare autoimmune vasculitis limited to the CNS often causing substantial disability. Understanding of this disease is impaired by the lack of available biomaterial. Here, we collected cerebrospinal fluid (CSF) from patients with PACNS and matched controls and performed unbiased proteomics profiling using ion mobility mass spectrometry to identify novel disease mechanisms and candidate biomarkers. We identified 14 candidate proteins, including amyloid-beta A4 protein (APP), with reduced abundance in the CSF of PACNS patients and validated APP by Enzyme-linked Immunosorbent Assay (ELISA) in an extended cohort of patients with PACNS. Subsequent functional annotation surprisingly suggested neuronal pathology rather than immune activation in PACNS. Our study is the first to employ mass spectrometry to local immune reactions in PACNS and it identifies candidates such as APP with pathogenic relevance in PACNS to improve patient care in the future.