Research progress on the role of vascular endothelial growth factor C signaling pathway in meningeal lymphatic-mediated beta-amyloid protein clearance

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the abnormal deposition of β-amyloid protein (Aβ) as its core pathology. Meningeal lymphatic vessels are crucial for Aβ clearance, and their dysfunction accelerates the progression of AD. Vascular endothelial growth factor-C (VEGF-C), through the activation of vascular endothelial growth factor receptor 3 and downstream pathways, synergistically promotes lymphangiogenesis, enhances endothelial permeability, and optimizes lymphatic dynamics, thereby significantly improving Aβ clearance efficiency. Genetic factors and age-related changes that lead to the attenuation of VEGF-C further impair meningeal lymphatic function, creating a vicious cycle. While VEGF-C intervention has shown cognitive improvements in AD models, clinical translation faces challenges such as non-specific activation of signaling pathways and individual differences. Future research should focus on the precise regulation of VEGF-C signaling and explore personalized AD treatment strategies based on meningeal lymphatic vessels. This paper reviews the molecular mechanisms, influencing factors, and intervention strategies through which VEGF-C regulates meningeal lymphatic vessel function to promote Aβ clearance, aiming to provide insights for AD research.