This study aimed to identify distinguishing indicators of aquaporin-4 (AQP4) IgG-negative NMOSD and assess their diagnostic value.<h4>Methods</h4>We analyzed four groups: 85 patients with AQP4-IgG-negative NMOSD, 192 with AQP4-IgG-positive NMOSD, 547 with other nervous system autoimmune disorders (e.g., multiple sclerosis, Guillain-Barré syndrome, and viral and autoimmune encephalitis), and 269 healthy controls matched for sex, age, and BMI.A diagnostic model was established using clinical, biochemical, and cerebrospinal fluid (CSF) variables. The gene discussed is AQP4; the disease is multiple sclerosis.