Neurovascular-immune-clearance remodeling in brain aging

Brain aging involves concurrent changes in cerebral vessels, immune regulation, and waste clearance, yet these processes are often studied separately. This fragmented approach limits understanding of how dysfunction in one system influences the others and contributes to age-related neurological disorders. This review summarizes current evidence on the neurovascular-immune-clearance axis, focusing on neurovascular unit deterioration, impaired glymphatic and meningeal lymphatic transport, neuroimmune remodeling, and the cell-specific mechanisms that connect these processes. We further compare their shared and disease-dependent roles in Alzheimer’s disease, vascular cognitive impairment, and late-life depression. Available imaging, fluid, proteomic, and epigenetic biomarkers are evaluated for their ability to measure different components of this axis, and emerging interventions are organized according to their predominant effects on vascular support, clearance function, immune signaling, and cellular senescence. Current evidence indicates that brain aging is characterized by interacting and partially compensable functional bottlenecks rather than a single linear pathological pathway. Integrating these mechanisms provides a framework for interpreting heterogeneous aging phenotypes, selecting complementary biomarkers, and developing mechanism-guided interventions. Future progress will depend on longitudinal human validation and direct demonstration that target engagement produces durable neurological benefit.