BACKGROUND: Alzheimer’s disease (AD) is increasingly linked to dysfunction of the meningeal lymphatic and glymphatic systems. Deep cervical lymphovenous anastomosis (dcLVA) is a microsurgical strategy to improve cervical lymphatic outflow whose mechanisms remain unclear.

METHODS: We established a dcLVA surgical intervention in App^NL−G−F rats and applied a multi-modal imaging and histological framework to assess clearance-related tracer transport, cerebral microvascular morphology and perfusion, and AD-related tissue changes.

RESULTS: The dcLVA improved behavior in AD rats. MRI tracer kinetic modeling showed alleviated glymphatic stasis and increased parenchymal influx. Hemodynamic showed restored arterial and venous perfusion toward normal levels. Increased cortical AQP4 polarization and was accompanied by marker-based shifts in microglia and astrocytes toward a less inflammatory and more reparative profile.

CONCLUSIONS: Our study demonstrates that dcLVA influences AD-related brain dysfunction by modulating downstream cervical lymphatic outflow and thereby reshaping coordinated aspects of clearance-related transport, microvascular perfusion, and glial homeostasis.