Neuroinflammation as a Final Common Pathway in Systemic Disease — How Systemic Disease Becomes Brain Disease

Purpose of review This chapter reviews evidence that neuroinflammation constitutes a final common pathway linking systemic disease of diverse origin to a shared spectrum of CNS injury, and synthesizes its mechanistic, biomarker, and therapeutic implications.Recent findings Autoimmune, infectious, metabolic, malignant, and age-related diseases converge on five shared CNS mechanisms-blood-brain barrier disruption, microglial priming, complement-mediated synaptic injury, microvascular and thromboinflammatory injury, and autoantibody-mediated neuronal targeting-that interact as a self-perpetuating loop rather than a linear cascade, with meningeal lymphatic and glymphatic clearance governing whether the cycle resolves or persists. These processes are increasingly measurable with non-disease-specific fluid biomarkers (IL-6, IL-1β, neurofilament light chain, GFAP) and imaging biomarkers (TSPO PET, vessel-wall and permeability MRI), and several are now targets of mechanism-directed therapy-IL-1 inhibition, complement blockade, blood-brain barrier stabilization, microglial modulation, and precision immunotherapy timed to disease stage. Recognizing neuroinflammation as this final common pathway reframes diagnosis around shared biomarkers rather than disease labels, predicts cross-disease therapeutic benefit, and relocates the therapeutic window earlier-toward protecting a brain vulnerable long before overt neurological disease declares itself.