Identification of a precise exit route for fluids leaving the brain, reported in Nature this week, helps us to understand how waste is cleared from the brain. The findings also shed light on how age-related changes in this process may affect the development of neurodegenerative diseases.
Excess fluids and large molecules (such as proteins) are removed from tissues via lymphatic vessels, although the brain was thought to lack a classical lymphatic drainage system until recently. Around four years ago a network of vessels (meningeal lymphatic vessels) in the outer brain membrane were rediscovered and found to regulate fluid balance by draining it of macromolecules. The precise route of cerebrospinal fluid (CSF) drainage remained unclear, however, in part due to difficulties in exploring a subset of these vessels trapped within complex structures at the base of the skull.
By performing careful examination of the skull base in mice, Gou Young Koh and colleagues visualize the precise location of basal meningeal lymphatic vessels and identify specialized features that facilitate CSF uptake and drainage. The authors compared meningeal lymphatic vessel structure and function in young (3 months old) and aged (24 - 27 months old) mice, uncovering an age-related decline in the vessel integrity and CSF clearance. A build-up of proteins in the brain is thought to contribute to age-related neurodegenerative diseases, such as Alzheimer’s disease. The latest findings provide further insights into the role of impaired CSF clearance in the development of neurodegenerative diseases.