In a case-control pilot study, we compared neuronal exosomes from the serum and/or plasma of healthy controls, controls with SLE without prior/active NPSLE (non-NPSLE), active NMDARE, and active NPSLE. Active disease was defined as <6 months from last new/worsening neuropsychiatric symptom. The NPSLE syndromes of interest included strokes, demyelination, cranial neuropathy, and aseptic meningitis. Demographics and clinical data were obtained for each participant. Biosamples underwent immunoprecipitation and immunopurification for neuron-derived exosomes using a patent-pending magnetic bead separation technique. Proteomic analysis was performed using liquid chromatography tandem mass spectrometry. Relative protein abundance was compared between disease/control groups with a false discovery rate (FDR) of <1% considered significant. Gene Set Enrichment Analysis was used to identify pathways that were up or downregulated in the disease states with FDR <25% considered significant.