Overview of the meningeal lymphatic vessels in aging and central nervous system disorders

In the aging process and central nervous system (CNS) diseases, the functions of the meningeal lymphatic vessels (MLVs) are impaired. Alterations in MLVs have been observed in aging-related neurodegenerative diseases, brain tumors, and even cerebrovascular disease. These findings reveal a new perspective on aging and CNS disorders and provide a promising therapeutic target. Additionally, recent neuropathological studies have shown that MLVs exchange soluble components between the cerebrospinal fluid (CSF) and interstitial fluid (ISF) and drain metabolites, cellular debris, misfolded proteins, and immune cells from the CSF into the deep cervical lymph nodes (dCLNs), directly connecting the brain with the peripheral circulation. Impairment and dysfunction of meningeal lymphatics can lead to the accumulation of toxic proteins in the brain, exacerbating the progression of neurological disorders. However, for many CNS diseases, the causal relationship between MLVs and neuropathological changes is not fully clear. Here, after a brief historical retrospection, we review recent discoveries about the hallmarks of MLVs and their roles in the aging and CNS diseases, as well as potential therapeutic targets for the treatment of neurologic diseases.