Neuroinflammation and humoral immunity across chronic diseases: mechanisms, biomarkers, and therapeutic implications

Abstract

Neuroinflammation and humoral immunity form an integrated, bidirectional framework underpinning the onset, progression, and treatment of major neurological diseases, including multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and stroke. All five neurological diseases show a clear, age-dependent increase in incidence. Neuroinflammatory cascades, driven by microglial and astrocytic activation, cytokine/chemokine networks, complement activation, and blood–brain barrier dysfunction, intersect with adaptive humoral mechanisms involving B-cells, immunoglobulins, and immune complexes. Although humoral and neuroinflammatory biomarkers have improved disease characterization, enabling earlier detection, patient stratification, and treatment monitoring, their broader clinical implementation remains limited by issues such as assay standardization and cross-platform reproducibility. The most reliable biomarkers highlight the importance of linking measurement strategies directly to the key biological mechanisms of each disease. Progress now depends on harmonized protocols, large-scale longitudinal validation, and integration of fluid biomarkers with imaging, genomic, and clinical phenotyping. Therapeutic strategies should be guided by stage-specific and endotype-specific biomarker profiles